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  • 1.
    Abdellah, Tebani
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Gummesson, Anders
    Zhong, Wen
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Koistinen, Ina Schuppe
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lakshmikanth, Tadepally
    Olsson, Lisa M.
    Boulund, Fredrik
    Neiman, Maja
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Stenlund, Hans
    Hellström, Cecilia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Karlsson, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Arif, Muhammad
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnkovic, Tea
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.
    Lee, Sunjae
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Zhang, Cheng
    Chen, Yang
    Olin, Axel
    Mikes, Jaromir
    Danielsson, Hanna
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Jansson, Per-Anders
    Angerås, Oskar
    Huss, Mikael
    Kjellqvist, Sanela
    Odeberg, Jacob
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Tremaroli, Valentina
    Forsström, Björn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Moritz, Thomas
    Bäckhed, Fredrik
    Engstrand, Lars
    Brodin, Petter
    Bergström, Göran
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Danish Tech Univ, Ctr Biosustainabil, Copenhagen, Denmark.
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Integration of molecular profiles in a longitudinal wellness profiling cohort2020Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 11, nr 1, artikkel-id 4487Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Abdellah, Tebani
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Normandie Univ, Dept Metab Biochem, UNIROUEN, INSERM,U1245,CHU Rouen, F-76000 Rouen, France..
    Jotanovic, Jelena
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Uppsala Univ Hosp, Dept Clin Pathol, Uppsala, Sweden..
    Hekmati, Neda
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Sivertsson, Åsa
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Gudjonsson, Olafur
    Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Engstrom, Britt Eden
    Uppsala Univ, Dept Med Sci Endocrinol & Mineral Metab, Uppsala, Sweden..
    Wikstrom, Johan
    Uppsala Univ, Dept Surg Sci, Neuroradiol, Uppsala, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Casar-Borota, Olivera
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.;Uppsala Univ Hosp, Dept Clin Pathol, Uppsala, Sweden..
    Ponten, Fredrik
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis2021Inngår i: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 9, nr 1, artikkel-id 181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.

  • 3. Adhikari, Subash
    et al.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Baker, Mark S.
    A high-stringency blueprint of the human proteome2020Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 11, nr 1, artikkel-id 5301Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases. The Human Proteome Project (HPP) was launched in 2010 to enhance accurate annotation of the genome-encoded proteome. Ten years later, the HPP releases its first blueprint of the human proteome, annotating 90% of all known proteins at high-stringency and discussing the implications of proteomics for precision medicine.

  • 4. Adori, Csaba
    et al.
    Barde, Swapnali
    Bogdanovic, Nenad
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Reinscheid, Rainer R.
    Kovacs, Gabor G.
    Hokfelt, Tomas
    Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons2015Inngår i: Frontiers in Neuroanatomy, E-ISSN 1662-5129, Vol. 9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal promoting effects of NPS make the NPS NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.

  • 5. Adori, Csaba
    et al.
    Barde, Swapnali
    Vas, Szilvia
    Ebner, Karl
    Su, Jie
    Svensson, Camilla
    Mathé, Aleksander A.
    Singewald, Nicolas
    Reinscheid, Rainer R.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Bagdy, Gyorgy
    Hökfelt, Tomas
    Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study2016Inngår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, nr 7, s. 3521-3546Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

  • 6.
    Adori, Csaba
    et al.
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Daraio, Teresa
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Kuiper, Raoul
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Barde, Swapnali
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Horvathova, Lubica
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia..
    Yoshitake, Takashi
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Ihnatko, Robert
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden.;Georg August Univ Gottingen, Univ Med Ctr, Inst Pathol, Gottingen, Germany..
    Valladolid-Acebes, Ismael
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Vercruysse, Pauline
    Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, Dept Mol Med & Surg, S-17176 Stockholm, Sweden..
    Wellendorf, Ashley M.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA..
    Gramignoli, Roberto
    Karolinska Inst, Dept Lab Med, S-17177 Stockholm, Sweden..
    Bozoky, Bela
    Karolinska Univ Hosp, Dept Clin Pathol Cytol, Huddinge, Sweden..
    Kehr, Jan
    Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden..
    Theodorsson, Elvar
    Linköping Univ, Dept Clin Chem, S-58285 Linköping, Sweden.;Linköping Univ, Dept Clin & Expt Med, S-58285 Linköping, Sweden..
    Cancelas, Jose A.
    Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.;Univ Cincinnati, Hoxworth Blood Ctr, Coll Med, Cincinnati, OH 45267 USA..
    Mravec, Boris
    Slovak Acad Sci, Biomed Res Ctr, Inst Expt Endocrinol, Bratislava, Slovakia.;Comenius Univ, Fac Med, Inst Physiol, Bratislava, Slovakia..
    Jorns, Carl
    Karolinska Univ Hosp Huddinge, PO Transplantat, S-14152 Stockholm, Sweden..
    Ellis, Ewa
    Karolinska Inst, Karolinska Univ Hosp, Dept Transplantat Surg, S-17177 Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol CLINTEC, S-17177 Stockholm, Sweden..
    Mulder, Jan
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden.;Royal Inst Technol, Sci Life Lab, S-10691 Stockholm, Sweden..
    Bark, Christina
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Hokfelt, Tomas
    Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden..
    Disorganization and degeneration of liver sympathetic innervations in nonalcoholic fatty liver disease revealed by 3D imaging2021Inngår i: Science Advances, E-ISSN 2375-2548, Vol. 7, nr 30, artikkel-id eabg5733Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

  • 7. Adori, Csaba
    et al.
    Glueck, Laura
    Barde, Swapnali
    Yoshitake, Takashi
    Kovacs, Gabor G.
    Mulder, Jan
    Magloczky, Zsofia
    Havas, Laszlo
    Boelcskei, Kata
    Mitsios, Nicholas
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Szolcsanyi, Janos
    Kehr, Jan
    Ronnback, Annica
    Schwartz, Thue
    Rehfeld, Jens F.
    Harkany, Tibor
    Palkovits, Miklos
    Schulz, Stefan
    Hokfelt, Tomas
    Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer's disease2015Inngår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, nr 4, s. 541-563Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.

  • 8.
    Adori, Monika
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Bhat, Sadam
    Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
    Gramignoli, Roberto
    Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Valladolid-Acebes, Ismael
    Department of Molecular Medicine and Surgery, The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
    Bengtsson, Tore
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Adori, Csaba
    Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), Stockholm University, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Hepatic Innervations and Nonalcoholic Fatty Liver Disease2023Inngår i: Seminars in liver disease (Print), ISSN 0272-8087, E-ISSN 1098-8971, Vol. 43, nr 2, s. 149-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abbreviations: VMN/PVN, hypothalamic ventromedial nucleus/paraventricular nucleus; VLM/VMM, ventrolateral medulla/ventromedial medulla; SMG/CG, superior mesenteric ganglion/caeliac ganglia; NTS, nucleus of the solitary tract; NG, nodose ganglion. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. Increased sympathetic (noradrenergic) nerve tone has a complex role in the etiopathomechanism of NAFLD, affecting the development/progression of steatosis, inflammation, fibrosis, and liver hemodynamical alterations. Also, lipid sensing by vagal afferent fibers is an important player in the development of hepatic steatosis. Moreover, disorganization and progressive degeneration of liver sympathetic nerves were recently described in human and experimental NAFLD. These structural alterations likely come along with impaired liver sympathetic nerve functionality and lack of adequate hepatic noradrenergic signaling. Here, we first overview the anatomy and physiology of liver nerves. Then, we discuss the nerve impairments in NAFLD and their pathophysiological consequences in hepatic metabolism, inflammation, fibrosis, and hemodynamics. We conclude that further studies considering the spatial-temporal dynamics of structural and functional changes in the hepatic nervous system may lead to more targeted pharmacotherapeutic advances in NAFLD.

  • 9. Agaton, C.
    et al.
    Galli, J.
    Guthenberg, I. H.
    Janzon, L.
    Hansson, M.
    Asplund, A.
    Brundell, E.
    Lindberg, S.
    Ruthberg, I.
    Wester, K.
    Wurtz, D.
    Hoog, C.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Ståhl, Stefan
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Ponten, F.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues2003Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 2, nr 6, s. 405-414Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.

  • 10.
    Agaton, Charlotta
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Falk, Ronny
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Hober, Sophia
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Selective enrichment of monospecific polyclonal antibodies for antibody-based proteomics efforts2004Inngår i: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1043, s. 33-40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A high stringency protocol, suitable for systematic purification of polyclonal antibodies, is described. The procedure is designed to allow the generation of target protein-specific antibodies suitable for functional annotation of proteins. Antibodies were generated by immunization with recombinantly produced affinity-tagged target proteins. To obtain stringent recovery of the antibodies, a two-step affinity chromatography principle was devised to first deplete the affinity tag-specific antibodies followed by a second step for affinity capture of the target protein-specific antibodies. An analytical dot-blot array system was developed to analyze the cross-reactivity of the affinity-purified antibodies. The results suggest that the protocol can be used in a highly parallel and automated manner to generate mono-specific polyclonal antibodies for large-scale, antibody-based proteomics efforts, i.e. affinity proteomics.

  • 11.
    Agaton, Charlotta
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Hober, Sophia
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Genome-based proteomics2004Inngår i: Electrophoresis, ISSN 0173-0835, E-ISSN 1522-2683, Vol. 25, nr 9, s. 1280-1288Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein-protein interactions play crucial roles in various biological pathways and functions. Therefore, the characterization of protein levels and also the network of interactions within an organism would contribute considerably to the understanding of life. The availability of the human genome sequence has created a range of new possibilities for biomedical research. A crucial challenge is to utilize the genetic information for better understanding of protein distribution and function in normal as well as in pathological biological processes. In this review, we have focused on different platforms used for systematic genome-based proteome analyses. These technologies are in many ways complementary and should be seen as various ways to elucidate different functions of the proteome.

  • 12.
    Agaton, Charlotta
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Unneberg, Per
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Sievertzon, Maria
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Holmberg, Anders
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Ehn, Maria
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Larsson, Magnus
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Odeberg, Jacob
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Gene expression analysis by signature pyrosequencing2002Inngår i: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 289, nr 1-2, s. 31-39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

     We describe a novel method for transcript profiling based on high-throughput parallel sequencing of signature tags using a non-gel-based microtiter plate format. The method relies on the identification of cDNA clones by pyrosequencing of the region corresponding to the 3'-end of the mRNA preceding the poly(A) tail. Simultaneously, the method can be used for gene discovery, since tags corresponding to unknown genes can be further characterized by extended sequencing. The protocol was validated using a model system for human atherosclerosis. Two 3'-tagged cDNA libraries, representing macrophages and foam cells, which are key components in the development of atherosclerotic plaques, were constructed using a solid phase approach. The libraries were analyzed by pyrosequencing, giving on average 25 bases. As a control, conventional expressed sequence tag (EST) sequencing using slab gel electrophoresis was performed. Homology searches were used to identify the genes corresponding to each tag. Comparisons with EST sequencing showed identical, unique matches in the majority of cases when the pyrosignature was at least 18 bases. A visualization tool was developed to facilitate differential analysis using a virtual chip format. The analysis resulted in identification of genes with possible relevance for development of atherosclerosis. The use of the method for automated massive parallel signature sequencing is discussed.

  • 13. Agnarsdottir, Margret
    et al.
    Sooman, Linda
    Bolander, Asa
    Stromberg, Sara
    Rexhepaj, Elton
    Bergqvist, Michael
    Ponten, Fredrik
    Gallagher, William
    Lennartsson, Johan
    Ekman, Simon
    Uhlen, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Skolan för bioteknologi (BIO), Centra, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Hedstrand, Hakan
    SOX10 expression in superficial spreading and nodular malignant melanomas2010Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, nr 6, s. 468-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P = 0.008). The staining intensity was also inversely correlated with T-stage (Spearman's rho = -0.261, P = 0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (rho = -0.173, P = 0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P <= 0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn. Melanoma Res 20:468-478

  • 14. Ahlin, G.
    et al.
    Hilgendorf, C.
    Karlsson, J.
    Al-Khalili Szigyarto, Cristina
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Artursson, P.
    Endogenous Gene and Protein Expression of Drug-Transporting Proteins in Cell Lines Routinely Used in Drug Discovery Programs2009Inngår i: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 37, nr 12, s. 2275-2283Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to investigate the gene and protein expression profiles of important drug-transporting proteins in human cell lines commonly used for studies of drug transport mechanisms. Human cell lines used to transiently or stably express single transporters [HeLa, human embryonic kidney (HEK) 293] and leukemia cell lines used to study drug resistance by ATP-binding cassette transporters (HL-60, K562) were investigated and compared with organotypic cell lines (HepG2, Saos-2, Caco-2, and Caco-2 TC7). For gene expression studies, real-time polymerase chain reaction was used, whereas monospecific polyclonal antibodies were generated and used to investigate protein expression by immunohistochemistry. Thirty-six transporters were studied for gene expression, and nine were studied for protein expression. The antibodies were validated using expression patterns in human tissues. Finally, the function of one ubiquitously expressed transporter, MCT1/SLC16A1, was investigated using [C-14]lactic acid as a substrate. In general, the adherent cell lines (HeLa, HEK293) displayed low transporter expression, and the expression patterns were barely affected by transfection. The leukemia cell lines (K562, HL-60) and Saos-2 also had low endogenous transporter expression, whereas the organotypic cell lines (HepG2 and Caco-2) showed higher expression of some transporters. Comparison of gene and protein expression profiles gave poor correlations, but better agreement was obtained for antibodies with a good validation score, indicating that antibody quality was a significant variable. It is noteworthy that the monocarboxylic acid-transporting protein MCT1 was significantly expressed in all and was functional in most of the cell lines, indicating that MCT1 may be a confounding factor when the transport of small anionic drugs is investigated.

  • 15. Ahmad, Yasmeen
    et al.
    Boisvert, Francois-Michel
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lamond, Angus I.
    Systematic Analysis of Protein Pools, Isoforms, and Modifications Affecting Turnover and Subcellular Localization2012Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 11, nr 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In higher eukaryotes many genes encode protein isoforms whose properties and biological roles are often poorly characterized. Here we describe systematic approaches for detection of either distinct isoforms, or separate pools of the same isoform, with differential biological properties. Using information from ion intensities we have estimated protein abundance levels and using rates of change in stable isotope labeling with amino acids in cell culture isotope ratios we measured turnover rates and subcellular distribution for the HeLa cell proteome. Protein isoforms were detected using three data analysis strategies that evaluate differences between stable isotope labeling with amino acids in cell culture isotope ratios for specific groups of peptides within the total set of peptides assigned to a protein. The candidate approach compares stable isotope labeling with amino acids in cell culture isotope ratios for predicted isoform- specific peptides, with ratio values for peptides shared by all the isoforms. The rule of thirds approach compares the mean isotope ratio values for all peptides in each of three equal segments along the linear length of the protein, assessing differences between segment values. The three in a row approach compares mean isotope ratio values for each sequential group of three adjacent peptides, assessing differences with the mean value for all peptides assigned to the protein. Protein isoforms were also detected and their properties evaluated by fractionating cell extracts on one- dimensional SDS- PAGE prior to trypsin digestion and MS analysis and independently evaluating isotope ratio values for the same peptides isolated from different gel slices. The effect of protein phosphorylation on turnover rates was analyzed by comparing mean turnover values calculated for all peptides assigned to a protein, either including, or excluding, values for cognate phosphopeptides. Collectively, these experimental and analytical approaches provide a framework for expanding the func- tional annotation of the genome.

  • 16.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Gharizadeh, B.
    Gustafsson, A. C.
    Sterky, Fredrik
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nyrén, Pål
    KTH, Tidigare Institutioner (före 2005), Biokemi och biokemisk teknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Single-nucleotide polymorphism analysis by pyrosequencing2000Inngår i: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 280, nr 1, s. 103-110Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a growing demand for high-throughput methods for analysis of single-nucleotide polymorphic (SNP) positions. Here, we have evaluated a novel sequencing approach, pyrosequencing, for such purposes. Pyrosequencing is a sequencing-by-synthesis method in which a cascade of enzymatic reactions yields detectable light, which is proportional to incorporated nucleotides. One feature of typing SNPs with pyrosequencing is that each allelic variant will give a unique sequence compared to the two other variants. These variants can easily be distinguished by a pattern recognition software. The software displays the allelic: alternatives and allows for direct comparison with the pyrosequencing raw data. For optimal determination of SNPs, various protocols of nucleotide dispensing order were investigated. Here, we demonstrate that typing of SNPs can efficiently be performed by pyrosequencing using an automated system for parallel analysis of 96 samples in approximately 5 min, suitable for large-scale screening and typing of SNPs.

  • 17.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nyrén, Pål
    KTH, Tidigare Institutioner (före 2005), Biokemi och biokemisk teknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Ronaghi, M.
    Analysis of the p53 tumor suppressor gene by pyrosequencing2000Inngår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 28, nr 1, s. 140-+Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tumor suppressor genes are implicated in cell cycle progression. Inactivation of these genes predominantly occurs through mutations and/or allelic loss that involves both alleles. With inactivation by multiple mutations in a single gene, cloning of the amplified gene is necessary to determine whether the mutations reside on one ol both alleles. Using pyrosequencing, a recently developed approach based on sequencing-by-synthesis, we studied genetic variability in the p53 tumor suppressor gene and could quantify the ratio between the mutated and wild-type amplified fragments. Further-more, this sequencing technique also allows allelic determination of adjacent mutations with no cloning of amplified fragments.

  • 18.
    Ahmadian, Afshin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Ren, Z P
    Williams, Cecilia
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, F
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Pontén, J
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Genetic instability in the 9q22.3 region is a late event in the development of squamous cell carcinoma.1998Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 17, nr 14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Squamous cell carcinoma (SCC) of the skin represents a group of neoplasms which is associated with exposure to UV light. Recently, we obtained data suggesting that invasive skin cancer and its precursors derive from one original neoplastic clone. Here, the analysis were extended by loss of heterozygosity (LOH) analysis in the chromosome 9q22.3 region. A total of 85 samples, taken from twenty-two sections of sun-exposed sites, corresponding to normal epidermis, morphological normal cells with positive immuno-staining for the p53 protein (p53 patches), dysplasias, cancer in situ (CIS) and squamous cell carcinomas (SCC) of the skin were analysed. Overall, about 70% of p53 patches had mutations in the p53 gene but not LOH in the p53 gene or 9q22.3 region. Approximately 70% of the dysplasias showed p53 mutations of which about 40% had LOH in the p53 region but not in the 9q22.3 region. In contrast, about 65% of SCC and CIS displayed LOH in the 9q22.3 region, as well as frequent (80%) mutations and/or LOH in the p53 gene. These findings strongly suggest that alterations in the p53 gene is an early event in the progression towards SCC, whereas malignant development involves LOH and alterations in at least one (or several) tumor suppressor genes located in chromosome 9q22.3.

  • 19.
    Ahmadian, Afshin
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Russom, Aman
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Andersson, Helene
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Stemme, Göran
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    SNP analysis by allele-specific extension in a micromachined filter chamber2002Inngår i: BioTechniques, ISSN 0736-6205, E-ISSN 1940-9818, Vol. 32, nr 4, s. 748-754Artikkel i tidsskrift (Fagfellevurdert)
  • 20.
    Akan, Pelin
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Alexeyenko, Andrey
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Costea, Paul Igor
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hedberg, Lilia
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Werne Solnestam, Beata
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundin, Sverker
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallman, Jimmie
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines2012Inngår i: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 4, s. 86-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.

  • 21.
    Al-Khalili Szigyarto, Cristina
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Persson, A.
    KTH.
    Berglund, L.
    KTH.
    Tourle, S.
    KTH. Royal Inst Technol, Stockholm, Sweden..
    Ekstrom, M.
    KTH.
    Lindskog, M.
    KTH.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    High throughput approach for bioinformatic design and cloning of protein epitope sequence tags suitable for antibody generation2005Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 4, nr 8, s. S60-S60Artikkel i tidsskrift (Annet vitenskapelig)
  • 22. Al-Khalili Szigyarto, Cristina
    et al.
    Sibbons, P.
    Williams, G.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Metcalfe, S. M.
    The E3 Ligase Axotrophin/MARCH-7: Protein Expression Profiling of Human Tissues Reveals Links to Adult Stem Cells2010Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 58, nr 4, s. 301-308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Axotrophin/MARCH-7 was first identified in mouse embryonic stem cells as a neural stem cell gene. Using the axotrophin/MARCH-7 null mouse, we discovered profound effects on T lymphocyte responses, including 8-fold hyperproliferation and 5-fold excess release of the stem cell cytokine leukemia inhibitory factor (LIF). Our further discovery that axotrophin/MARCH-7 is required for targeted degradation of the LIF receptor subunit gp190 implies a direct role in the regulation of LIF signaling. Bioinformatics studies revealed a highly conserved RING-CH domain in common with the MARCH family of E3-ubiquitin ligases, and accordingly, axotrophin was renamed "MARCH-7." To probe protein expression of human axotrophin/MARCH-7, we prepared antibodies against different domains of the protein. Each antibody bound its specific target epitope with high affinity, and immunohistochemistry cross-validated target specificity. Forty-eight human tissue types were screened. Epithelial cells stained strongly, with trophoblasts having the greatest staining. In certain tissues, specific cell types were selectively positive, including neurons and neuronal progenitor cells in the hippocampus and cerebellum, endothelial sinusoids of the spleen, megakaryocytes in the bone marrow, crypt stem cells of the small intestine, and alveolar macrophages in the 7 lung. Approximately 20% of central nervous system neuropils were positive. Notably, axotrophin/MARCH-7 has an expression profile that is distinct from that of other MARCH family members. This manuscript contains online supplemental material at http://www.jhc. org. Please visit this article online to view these materials. (J Histochem Cytochem 58:301-308, 2010)

  • 23.
    Alm, Tove L.
    et al.
    KTH, Skolan för bioteknologi (BIO).
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO).
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO).
    The Affinity Binder Knockdown Initiative2015Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 26Artikkel i tidsskrift (Annet vitenskapelig)
  • 24.
    Alm, Tove L.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Lundberg, Emma
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    The Affinity Binder Knockdown Initiative.2016Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 27Artikkel i tidsskrift (Fagfellevurdert)
  • 25.
    Alm, Tove L.
    et al.
    KTH, Skolan för bioteknologi (BIO).
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO).
    Antibodypedia - The wiki of antibodies2015Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 26Artikkel i tidsskrift (Annet vitenskapelig)
  • 26.
    Alm, Tove L.
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    von Feilitzen, Kalle
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    ANTIBODYPEDIA: THE WIKI OF ANTIBODIES2016Inngår i: Molecular Biology of the Cell, ISSN 1059-1524, E-ISSN 1939-4586, Vol. 27Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Alm, Tove
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Introducing the Affinity Binder Knockdown Initiative-A public-private partnership for validation of affinity reagents2016Inngår i: EuPA Open Proteomics, E-ISSN 2212-9685, Vol. 10, s. 56-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The newly launched Affinity Binder Knockdown Initiative encourages antibody suppliers and users to join this public-private partnership, which uses crowdsourcing to collect characterization data on antibodies. Researchers are asked to share validation data from experiments where gene-editing techniques (such as siRNA or CRISPR) have been used to verify antibody binding. The initiative is launched under the aegis of Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies towards human protein targets. What is known about an antibody is the foundation of the scoring and ranking system in Antibodypedia.

  • 28.
    Alm, Tove
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    von Feilitzen, Kalle
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Lundberg, Emma
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sivertsson, Åsa
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    A Chromosome-Centric Analysis of Antibodies Directed toward the Human Proteome Using Antibodypedia2014Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, nr 3, s. 1669-1676Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibodies are crucial for the study of human proteins and have been defined as one of the three pillars in the human chromosome-centric Human Proteome Project (CHPP). In this article the chromosome-centric structure has been used to analyze the availability of antibodies as judged by the presence within the portal Antibodypedia, a database designed to allow comparisons and scoring of publicly available antibodies toward human protein targets. This public database displays antibody data from more than one million antibodies toward human protein targets. A summary of the content in this knowledge resource reveals that there exist more than 10 antibodies to over 70% of all the putative human genes, evenly distributed over the 24 human chromosomes. The analysis also shows that at present, less than 10% of the putative human protein-coding genes (n = 1882) predicted from the genome sequence lack antibodies, suggesting that focused efforts from the antibody-based and mass spectrometry-based proteomic communities should be encouraged to pursue the analysis of these missing proteins. We show that Antibodypedia may be used to track the development of available and validated antibodies to the individual chromosomes, and thus the database is an attractive tool to identify proteins with no or few antibodies yet generated.

  • 29.
    Altay, Özlem
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Department of Clinical Microbiology, Dr Sami Ulus Training and Research Hospital, University of Health Sciences, Ankara, 06080 Turkey.
    Arif, Muhammad
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Li, Xiangyu
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Yang, Hong
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Aydın, M.
    Department of Infectious Diseases, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, 34766 Turkey.
    Alkurt, G.
    Genomic Laboratory (GLAB), Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, 34766 Turkey.
    Kim, Woonghee
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Akyol, D.
    Genomic Laboratory (GLAB), Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, 34766 Turkey.
    Zhang, Cheng
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan, 450001 P. R. China.
    Dinler-Doganay, G.
    Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, 34469 Turkey.
    Turkez, H.
    Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, 34469 Turkey.
    Shoaie, Saeed
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 1UL UK.
    Nielsen, J.
    Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, SE-41296 Sweden.
    Borén, J.
    Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital Gothenburg, Gothenburg, SE-41345 Sweden.
    Olmuscelik, O.
    Department of Internal Medicine, Istanbul Medipol University, Bagcılar, Istanbul, 34214 Turkey.
    Doganay, L.
    Department of Gastroenterology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, 34766 Turkey.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London, SE1 1UL UK.
    Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-192021Inngår i: Advanced Science, E-ISSN 2198-3844, Vol. 8, nr 17, artikkel-id 2101222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

  • 30.
    Altay, Özlem
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mohammadi, Elyas
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Ferdowsi Univ Mashhad, Dept Anim Sci, Mashhad 9177948974, Razavi Khorasan, Iran..
    Lam, Simon
    Kings Coll London, Ctr Host Microbiome Interact, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England..
    Turkez, Hasan
    Ataturk Univ, Dept Med Biol, Fac Med, TR-25240 Erzurum, Turkey..
    Boren, Jan
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, S-41345 Gothenburg, Sweden..
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Se Gothenburg, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Kings Coll London, Ctr Host Microbiome Interact, Fac Dent Oral & Craniofacial Sci, London SE1 9RT, England..
    Current Status of COVID-19 Therapies and Drug Repositioning Applications2020Inngår i: iScience, E-ISSN 2589-0042 , Vol. 23, nr 7, artikkel-id 101303Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2.

  • 31.
    Altay, Özlem
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Boren, Jan
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Gothenburg, Sweden..
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Systems biology perspective for studying the gut microbiota in human physiology and liver diseases2019Inngår i: EBioMedicine, E-ISSN 2352-3964, Vol. 49, s. 364-373Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The advancement in high-throughput sequencing technologies and systems biology approaches have revolutionized our understanding of biological systems and opened a new path to investigate unacknowledged biological phenomena. In parallel, the field of human microbiome research has greatly evolved and the relative contribution of the gut microbiome to health and disease have been systematically explored. This review provides an overview of the network-based and translational systems biology-based studies focusing on the function and composition of gut microbiota. We also discussed the association between the gut microbiome and the overall human physiology, as well as hepatic diseases and other metabolic disorders.

  • 32.
    Altay, Özlem
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. Department of Clinical Microbiology, Sami Ulus Training and Research Hospital, University of Health Sciences, Ankara, 06080, Turkey.
    Zhang, Cheng
    Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China..
    Turkez, Hasan
    Ataturk Univ, Fac Med, Dept Med Biol, TR-25240 Erzurum, Turkey..
    Nielsen, Jens
    Chalmers Univ Technol, Dept Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. King’s College London, London, SE1 9RT, United Kingdom.
    Revealing the Metabolic Alterations during Biofilm Development of Burkholderia cenocepacia Based on Genome-Scale Metabolic Modeling2021Inngår i: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 11, nr 4, artikkel-id 221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Burkholderia cenocepacia is among the important pathogens isolated from cystic fibrosis (CF) patients. It has attracted considerable attention because of its capacity to evade host immune defenses during chronic infection. Advances in systems biology methodologies have led to the emergence of methods that integrate experimental transcriptomics data and genome-scale metabolic models (GEMs). Here, we integrated transcriptomics data of bacterial cells grown on exponential and biofilm conditions into a manually curated GEM of B. cenocepacia. We observed substantial differences in pathway response to different growth conditions and alternative pathway susceptibility to extracellular nutrient availability. For instance, we found that blockage of the reactions was vital through the lipid biosynthesis pathways in the exponential phase and the absence of microenvironmental lysine and tryptophan are essential for survival. During biofilm development, bacteria mostly had conserved lipid metabolism but altered pathway activities associated with several amino acids and pentose phosphate pathways. Furthermore, conversion of serine to pyruvate and 2,5-dioxopentanoate synthesis are also identified as potential targets for metabolic remodeling during biofilm development. Altogether, our integrative systems biology analysis revealed the interactions between the bacteria and its microenvironment and enabled the discovery of antimicrobial targets for biofilm-related diseases.

  • 33.
    Alvez, Maria Bueno
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Edfors, Fredrik
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    von Feilitzen, Kalle
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zwahlen, Martin
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London, SE1 9RT, UK.
    Edqvist, Per Henrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Sjöblom, Tobias
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lundin, Emma
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Rameika, Natallia
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Enblad, Gunilla
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lindman, Henrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Höglund, Martin
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hesselager, Göran
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Stålberg, Karin
    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
    Enblad, Malin
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Simonson, Oscar E.
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Häggman, Michael
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Axelsson, Tomas
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Åberg, Mikael
    Department of Medical Sciences, Clinical Chemistry and SciLifeLab Affinity Proteomics, Uppsala University, Uppsala, Sweden.
    Nordlund, Jessica
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Zhong, Wen
    Science for Life Laboratory, Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
    Karlsson, Max
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Gyllensten, Ulf
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Ponten, Fredrik
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Next generation pan-cancer blood proteome profiling using proximity extension assay2023Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 14, nr 1, artikkel-id 4308Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.

  • 34.
    Andersson, Anders
    et al.
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Keskitalo, J.
    Sjödin, A.
    Bhalerao, Rupali
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Sterky, Fredrik
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Wissel, K.
    Tandre, K.
    Aspeborg, Henrik
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Moyle, R.
    Ohmiya, Y.
    Brunner, A.
    Gustafsson, P.
    Karlsson, J.
    Lundeberg, Joakim
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Nilsson, O.
    Sandberg, G.
    Strauss, S.
    Sundberg, B.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    Jansson, S.
    Nilsson, Peter
    KTH, Tidigare Institutioner (före 2005), Bioteknologi.
    A transcriptional timetable of autumn senescence2004Inngår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 5, nr 4, s. R24-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We have developed genomic tools to allow the genus Populus ( aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag ( EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results: On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree ( Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions: We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.

  • 35. Andersson, Ann-Catrin
    et al.
    Stromberg, Sara
    Backvall, Helena
    Kampf, Caroline
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Wester, Kenneth
    Ponten, Fredrik
    Analysis of protein expression in cell microarrays: A tool for antibody-based proteomics2006Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 54, nr 12, s. 1413-1423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tissue microarray (TMA) technology provides a possibility to explore protein expression patterns in a multitude of normal and disease tissues in a high-throughput setting. Although TMAs have been used for analysis of tissue samples, robust methods for studying in vitro cultured cell lines and cell aspirates in a TMA format have been lacking. We have adopted a technique to homogeneously distribute cells in an agarose gel matrix, creating an artificial tissue. This enables simultaneous profiling of protein expression in suspension- and adherent-grown cell samples assembled in a microarray. In addition, the present study provides an optimized strategy for the basic laboratory steps to efficiently produce TMAs. Presented modifications resulted in an improved quality of specimens and a higher section yield compared with standard TMA production protocols. Sections from the generated cell TMAs were tested for immunohistochemical staining properties using 20 well-characterized antibodies. Comparison of immunoreactivity in cultured dispersed cells and corresponding cells in tissue samples showed congruent results for all tested antibodies. We conclude that a modified TIVIA technique, including cell samples, provides a valuable tool for high-throughput analysis of protein expression, and that this technique can be used for global approaches to explore the human proteome.

  • 36.
    Andersson, Annika
    et al.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Remnestål, Julia
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nellgård, B.
    Vunk, Helian
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Kotol, David
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Edfors, Fredrik
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Schwenk, Jochen M.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Ilag, L. L.
    Zetterberg, H.
    Blennow, K.
    Månberg, Anna
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Nilsson, Peter
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap.
    Fredolini, Claudia
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Affinitets-proteomik.
    Development of parallel reaction monitoring assays for cerebrospinal fluid proteins associated with Alzheimer's disease2019Inngår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 494, s. 79-93Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Detailed knowledge of protein changes in cerebrospinal fluid (CSF) across healthy and diseased individuals would provide a better understanding of the onset and progression of neurodegenerative disorders. In this study, we selected 20 brain-enriched proteins previously identified in CSF by antibody suspension bead arrays (SBA) to be potentially biomarkers for Alzheimer's disease (AD) and verified these using an orthogonal approach. We examined the same set of 94 CSF samples from patients affected by AD (including preclinical and prodromal), mild cognitive impairment (MCI), non-AD dementia and healthy individuals, which had previously been analyzed by SBA. Twenty-eight parallel reaction monitoring (PRM) assays were developed and 13 of them could be validated for protein quantification. Antibody profiles were verified by PRM. For seven proteins, the antibody profiles were highly correlated with the PRM results (r > 0.7) and GAP43, VCAM1 and PSAP were identified as potential markers of preclinical AD. In conclusion, we demonstrate the usefulness of targeted mass spectrometry as a tool for the orthogonal verification of antibody profiling data, suggesting that these complementary methods can be successfully applied for comprehensive exploration of CSF protein levels in neurodegenerative disorders.

  • 37. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Björn
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Segersten, Ulrika
    Malmström, Per-Uno
    Jirström, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014Inngår i: BMC Urology, E-ISSN 1471-2490, Vol. 14, nr 1, s. 36-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

  • 38. Andersson, Sandra
    et al.
    Nilsson, Kenneth
    Fagerberg, Linn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sundström, Christer
    Danielsson, Angelika
    Edlund, Karolina
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Asplund, Anna
    The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues2014Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 12, s. e115911-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.

  • 39.
    Andrade, Jorge
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Berglund, Lisa
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Using Grid Technology for Computationally Intensive Applied Bioinformatics Analyses2006Inngår i: In Silico Biology, ISSN 1386-6338, Vol. 6, nr 6, s. 495-504Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For several applications and algorithms used in applied bioinformatics, a bottle neck in terms of computational time may arise when scaled up to facilitate analyses of large datasets and databases. Re-codification, algorithm modification or sacrifices in sensitivity and accuracy may be necessary to accommodate for limited computational capacity of single work stations. Grid computing offers an alternative model for solving massive computational problems by parallel execution of existing algorithms and software implementations. We present the implementation of a Grid-aware model for solving computationally intensive bioinformatic analyses exemplified by a blastp sliding window algorithm for whole proteome sequence similarity analysis, and evaluate the performance in comparison with a local cluster and a single workstation. Our strategy involves temporary installations of the BLAST executable and databases on remote nodes at submission, accommodating for dynamic Grid environments as it avoids the need of predefined runtime environments (preinstalled software and databases at specific Grid-nodes). Importantly, the implementation is generic where the BLAST executable can be replaced by other software tools to facilitate analyses suitable for parallelisation. This model should be of general interest in applied bioinformatics. Scripts and procedures are freely available from the authors.

  • 40. Andrews, B. J.
    et al.
    Marian Walhout, A. J.
    Iyengar, R.
    Apweiler, R.
    Ardlie, K.
    Azeloglu, E. U.
    Birtwistle, M. R.
    Coon, J. J.
    Dolinski, K.
    Fan, T.
    FitzGerald, G. A.
    Gavin, A. -C
    Gingras, A. -C
    Gough, N. R.
    Hoffmann, A.
    Lee, M. J.
    Loew, L. M.
    CraigMak, H.
    Murphy, R. C.
    Myers, C.
    Snyder, M. P.
    Sorger, P. K.
    Stolovitzky, G.
    Subramaniam, S.
    Taipale, M.
    Travé, G.
    Troyanskaya, O. G.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Vidal, M.
    Quantitative human cell encyclopedia2016Inngår i: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 9, nr 443, artikkel-id mr1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Scientists gathered to discuss the necessity, feasibility, and challenges of generating a quantitative catalog of the components in human cells that is essential for our understanding of human physiology in health and disease and to support future breakthroughs in treating diseases. This report summarizes the discussion that emerged at the Human Quantitative Dynamics Workshop held in Bethesda, MD, USA, in December 2015.

  • 41.
    Anfelt, Josefine
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hallström, Björn
    Nielsen, Jens
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Hudson, Elton Paul
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Using Transcriptomics To Improve Butanol Tolerance of Synechocystis sp Strain PCC 68032013Inngår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 79, nr 23, s. 7419-7427Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cyanobacteria are emerging as promising hosts for production of advanced biofuels such as n-butanol and alkanes. However, cyanobacteria suffer from the same product inhibition problems as those that plague other microbial biofuel hosts. High concentrations of butanol severely reduce growth, and even small amounts can negatively affect metabolic processes. An understanding of how cyanobacteria are affected by their biofuel product can enable identification of engineering strategies for improving their tolerance. Here we used transcriptome sequencing (RNA-Seq) to assess the transcriptome response of Synechocystis sp. strain PCC 6803 to two concentrations of exogenous n-butanol. Approximately 80 transcripts were differentially expressed at 40 mg/liter butanol, and 280 transcripts were different at 1 g/liter butanol. Our results suggest a compromised cell membrane, impaired photosynthetic electron transport, and reduced biosynthesis. Accumulation of intracellular reactive oxygen species (ROS) scaled with butanol concentration. Using the physiology and transcriptomics data, we selected several genes for overexpression in an attempt to improve butanol tolerance. We found that overexpression of several proteins, notably, the small heat shock protein HspA, improved tolerance to butanol. Transcriptomics-guided engineering created more solvent-tolerant cyanobacteria strains that could be the foundation for a more productive biofuel host.

  • 42.
    Anfelt, Josefine
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Kaczmarzyk, Danuta
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Shabestary, Kiyan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Renberg, Björn
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Rockberg, Johan
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Nielsen, Jens
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. Tech Univ Denmark.
    Hudson, Elton P.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi.
    Genetic and nutrient modulation of acetyl-CoA levels in Synechocystis for n-butanol production2015Inngår i: Microbial Cell Factories, ISSN 1475-2859, E-ISSN 1475-2859, Vol. 14, artikkel-id 167Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: There is a strong interest in using photosynthetic cyanobacteria as production hosts for biofuels and chemicals. Recent work has shown the benefit of pathway engineering, enzyme tolerance, and co-factor usage for improving yields of fermentation products. Results: An n-butanol pathway was inserted into a Synechocystis mutant deficient in polyhydroxybutyrate synthesis. We found that nitrogen starvation increased specific butanol productivity up to threefold, but cessation of cell growth limited total n-butanol titers. Metabolite profiling showed that acetyl-CoA increased twofold during nitrogen starvation. Introduction of a phosphoketolase increased acetyl-CoA levels sixfold at nitrogen replete conditions and increased butanol titers from 22 to 37 mg/L at day 8. Flux balance analysis of photoautotrophic metabolism showed that a Calvin-Benson-Bassham-Phosphoketolase pathway had higher theoretical butanol productivity than CBB-Embden-Meyerhof-Parnas and a reduced butanol ATP demand. Conclusion: These results demonstrate that phosphoketolase overexpression and modulation of nitrogen levels are two attractive routes toward increased production of acetyl-CoA derived products in cyanobacteria and could be implemented with complementary metabolic engineering strategies.

  • 43.
    Ardalan, Arman
    et al.
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Kluetsch, Cornelya F. C.
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för bioteknologi (BIO), Genteknologi.
    Zhang, Ai-bing
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Erdogan, Metin
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik.
    Houshmand, Massoud
    Tepeli, Cafer
    Ashtiani, Seyed Reza Miraei
    Savolainen, Peter
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent domestication of wolf, but implies dog–wolf hybridization2011Inngår i: Ecology and Evolution, E-ISSN 2045-7758, Vol. 1, nr 3, s. 373-385Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies of mitochondrial DNA (mtDNA) diversity indicate explicitly that dogs were domesticated, probably exclusively, in southern East Asia. However, Southwest Asia (SwAsia) has had poor representation and geographical coverage in these studies. Other studies based on archaeological and genome-wide SNP data have suggested an origin of dogs in SwAsia. Hence, it has been suspected that mtDNA evidence for this scenario may have remained undetected. In the first comprehensive investigation of genetic diversity among SwAsian dogs, we analyzed 582 bp of mtDNA for 345 indigenous dogs from across SwAsia, and compared with 1556 dogs across the Old World. We show that 97.4% of SwAsian dogs carry haplotypes belonging to a universal mtDNA gene pool, but that only a subset of this pool, five of the 10 principal haplogroups, is represented in SwAsia. A high frequency of haplogroup B, potentially signifying a local origin, was not paralleled with the high genetic diversity expected for a center of origin. Meanwhile, 2.6% of the SwAsian dogs carried the rare non-universal haplogroup d2. Thus, mtDNA data give no indication that dogs originated in SwAsia through independent domestication of wolf, but dog–wolf hybridization may have formed the local haplogroup d2 within this region. Southern East Asia remains the only region with virtually full extent of genetic variation, strongly indicating it to be the primary and probably sole center of wolf domestication. An origin of dogs in southern East Asia may have been overlooked by other studies due to a substantial lack of samples from this region.

  • 44.
    Arif, Muhammad
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Klevstig, Martina
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.
    Benfeitas, Rui
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Doran, Stephen
    Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London, England.
    Turkez, Hasan
    Ataturk Univ, Fac Med, Dept Med Biol, Erzurum, Turkey.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Clausen, Maryam
    AstraZeneca, Translat Genom BioPharmaceut R & Discovery Sci, Gothenburg, Sweden.
    Wikström, Johannes
    AstraZeneca, Biosci Cardiovasc Res & Early Dev Cardiovasc Rena, BioPharmaceut R&D, Gothenburg, Sweden.
    Etal, Damla
    AstraZeneca, Translat Genom BioPharmaceut R & Discovery Sci, Gothenburg, Sweden.
    Zhang, Cheng
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Levin, Malin
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Boren, Jan
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Mol & Clin Med, Wallenberg Lab, Gothenburg, Sweden.
    Integrative transcriptomic analysis of tissue-specific metabolic crosstalk after myocardial infarction2021Inngår i: eLIFE, E-ISSN 2050-084X, Vol. 10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genome-wide transcriptomic analysis on tissue samples obtained 6- and 24-hours post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI; and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.Competing Interest StatementJW, MC, DE are employees at AstraZeneca. The other authors declare no conflict of interest.

  • 45.
    Arif, Muhammad
    et al.
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Zhang, Cheng
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou University, Zhengzhou, Henan Province, PR 450001, China.
    Li, Xiangyu
    KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Güngör, Cem
    Çakmak, Buğra
    Arslantürk, Metin
    Tebani, Abdellah
    Özcan, Berkay
    Subaş, Oğuzhan
    Zhou, Wenyu
    Piening, Brian
    Turkez, Hasan
    Fagerberg, Linn
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Price, Nathan
    Hood, Leroy
    Snyder, Michael
    Nielsen, Jens
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Mardinoglu, Adil
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi. Centre for Host–Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK.
    iNetModels 2.0: an interactive visualization and database of multi-omics data.2021Inngår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 49, nr W1, s. W271-W276, artikkel-id gkab254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It is essential to reveal the associations between various omics data for a comprehensive understanding of the altered biological process in human wellness and disease. To date, very few studies have focused on collecting and exhibiting multi-omics associations in a single database. Here, we present iNetModels, an interactive database and visualization platform of Multi-Omics Biological Networks (MOBNs). This platform describes the associations between the clinical chemistry, anthropometric parameters, plasma proteomics, plasma metabolomics, as well as metagenomics for oral and gut microbiome obtained from the same individuals. Moreover, iNetModels includes tissue- and cancer-specific Gene Co-expression Networks (GCNs) for exploring the connections between the specific genes. This platform allows the user to interactively explore a single feature's association with other omics data and customize its particular context (e.g. male/female specific). The users can also register their data for sharing and visualization of the MOBNs and GCNs. Moreover, iNetModels allows users who do not have a bioinformatics background to facilitate human wellness and disease research. iNetModels can be accessed freely at https://inetmodels.com without any limitation.

  • 46.
    Asplund, C.
    et al.
    KTH.
    Uhlén, Mathias
    KTH, Tidigare Institutioner (före 2005), Bioteknologi. Royal Inst Technol, Stockholm, Sweden..
    Lundeberg, Joakim
    KTH.
    Persson, A.
    KTH.
    Real-time RT-PCR of protein epitope signature tags2005Inngår i: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 4, nr 8, s. S60-S60Artikkel i tidsskrift (Annet vitenskapelig)
  • 47. Attems, Johannes
    et al.
    Alpar, Alan
    Spence, Lauren
    McParland, Shane
    Heikenwalder, Mathias
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Tanila, Heikki
    Hökfelt, Tomas G. M.
    Harkany, Tibor
    Clusters of secretagogin-expressing neurons in the aged human olfactory tract lack terminal differentiation2012Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, nr 16, s. 6259-6264Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Expanding the repertoire of molecularly diverse neurons in the human nervous system is paramount to characterizing the neuronal networks that underpin sensory processing. Defining neuronal identities is particularly timely in the human olfactory system, whose structural differences from nonprimate macrosmatic species have recently gained momentum. Here, we identify clusters of bipolar neurons in a previously unknown outer "shell" domain of the human olfactory tract, which express secretagogin, a cytosolic Ca2+ binding protein. These "shell" neurons are wired into the olfactory circuitry because they can receive mixed synaptic inputs. Unexpectedly, secretagogin is often coexpressed with polysialylated-neural cell adhesion molecule, beta-III-tubulin, and calretinin, suggesting that these neurons represent a cell pool that might have escaped terminal differentiation into the olfactory circuitry. We hypothesized that secretagogin-containing "shell" cells may be eliminated from the olfactory axis under neurodegenerative conditions. Indeed, the density, but not the morphological or neurochemical integrity, of secretagogin-positive neurons selectively decreases in the olfactory tract in Alzheimer's disease. In conclusion, secretagogin identifies a previously undescribed cell pool whose cytoarchitectonic arrangements and synaptic connectivity are poised to modulate olfactory processing in humans.

  • 48. Auffray, C.
    et al.
    Balling, R.
    Blomberg, N.
    Bonaldo, M. C.
    Boutron, B.
    Brahmachari, S.
    Bréchot, C.
    Cesario, A.
    Chen, S. -J
    Clément, K.
    Danilenko, D.
    Meglio, A. D.
    Gelemanović, A.
    Goble, C.
    Gojobori, T.
    Goldman, J. D.
    Goldman, M.
    Guo, Y. -K
    Heath, J.
    Hood, L.
    Hunter, P.
    Jin, L.
    Kitano, H.
    Knoppers, B.
    Lancet, D.
    Larue, C.
    Lathrop, M.
    Laville, M.
    Lindner, A. B.
    Magnan, A.
    Metspalu, A.
    Morin, E.
    Ng, L. F. P.
    Nicod, L.
    Noble, D.
    Nottale, L.
    Nowotny, H.
    Ochoa, T.
    Okeke, I. N.
    Oni, T.
    Openshaw, P.
    Oztürk, M.
    Palkonen, S.
    Paweska, J. T.
    Pison, C.
    Polymeropoulos, M. H.
    Pristipino, C.
    Protzer, U.
    Roca, J.
    Rozman, D.
    Santolini, M.
    Sanz, F.
    Scambia, G.
    Segal, E.
    Serageldin, I.
    Soares, M. B.
    Sterk, P.
    Sugano, S.
    Superti-Furga, G.
    Supple, D.
    Tegner, J.
    Uhlén, Mathias
    KTH, Centra, Science for Life Laboratory, SciLifeLab. KTH, Skolan för kemi, bioteknologi och hälsa (CBH), Proteinvetenskap, Systembiologi.
    Urbani, A.
    Valencia, A.
    Valentini, V.
    van der Werf, S.
    Vinciguerra, M.
    Wolkenhauer, O.
    Wouters, E.
    COVID-19 and beyond: a call for action and audacious solidarity to all the citizens and nations, it is humanity’s fight2020Inngår i: F1000 Research, E-ISSN 2046-1402, Vol. 9, s. 1130-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies. 

  • 49.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Birgersson, Elin
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Mezger, Anja
    Nilsson, Mats
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Multiplexed protein profiling by sequential affinity capture2016Inngår i: Proteomics, ISSN 1615-9853, E-ISSN 1615-9861, Vol. 16, nr 8, s. 1251-1256Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibody microarrays enable parallelized and miniaturized analysis of clinical samples, and have proven to provide novel insights for the analysis of different proteomes. However, there are concerns that the performance of such direct labeling and single antibody assays are prone to off-target binding due to the sample context. To improve selectivity and sensitivity while maintaining the possibility to conduct multiplexed protein profiling, we developed a multiplexed and semi-automated sequential capture assay. This novel bead-based procedure encompasses a first antigen capture, labeling of captured protein targets on magnetic particles, combinatorial target elution and a read-out by a secondary capture bead array. We demonstrate in a proof-of-concept setting that target detection via two sequential affinity interactions reduced off-target contribution, while lowered background and noise levels, improved correlation to clinical values compared to single binder assays. We also compared sensitivity levels with single binder and classical sandwich assays, explored the possibility for DNA-based signal amplification, and demonstrate the applicability of the dual capture bead-based antibody microarray for biomarker analysis. Hence, the described concept enhances the possibilities for antibody array assays to be utilized for protein profiling in body fluids and beyond.

  • 50.
    Ayoglu, Burcu
    et al.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Chaouch, Amina
    Lochmüller, Hanns
    Politano, Luisa
    Bertini, Enrico
    Spitali, Pietro
    Hiller, Monika
    Niks, Eric H.
    Gualandi, Francesca
    Pontén, Fredrik
    Bushby, Kate
    Aartsma-Rus, Annemieke
    Schwartz, Elena
    Le Priol, Yannick
    Straub, Volker
    Uhlén, Mathias
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Cirak, Sebahattin
    't Hoen, Peter A. C.
    Muntoni, Francesco
    Ferlini, Alessandra
    Schwenk, Jochen M.
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Nilsson, Peter
    KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Szigyarto, Cristina Al-Khalili
    Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies2014Inngår i: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 6, nr 7, s. 918-936Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavo-protein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.

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