%0 Journal Article %1 Uhlen2015Tissuebased %A Uhlén, Mathias %A Fagerberg, Linn %A Hallström, Björn M. %A Lindskog, Cecilia %A Oksvold, Per %A Mardinoglu, Adil %A Sivertsson, \AAsa %A Kampf, Caroline %A Sjöstedt, Evelina %A Asplund, Anna %A Olsson, IngMarie %A Edlund, Karolina %A Lundberg, Emma %A Navani, Sanjay %A Szigyarto, Cristina A. %A Odeberg, Jacob %A Djureinovic, Dijana %A Takanen, Jenny O. %A Hober, Sophia %A Alm, Tove %A Edqvist, Per-Henrik %A Berling, Holger %A Tegel, Hanna %A Mulder, Jan %A Rockberg, Johan %A Nilsson, Peter %A Schwenk, Jochen M. %A Hamsten, Marica %A von Feilitzen, Kalle %A Forsberg, Mattias %A Persson, Lukas %A Johansson, Fredric %A Zwahlen, Martin %A von Heijne, Gunnar %A Nielsen, Jens %A Pontén, Fredrik %D 2015 %I American Association for the Advancement of Science %J Science %K human protein-protein-interactions %N 6220 %P 1260419 %R 10.1126/science.1260419 %T Tissue-based map of the human proteome %U http://dx.doi.org/10.1126/science.1260419 %V 347 %X Reconstruction of human generic and condition-specific metabolic models. Identifying metabolic differences through comparing flux distributions using constraint-based modeling. Identifying disease-specific metabolic characters in metabolic disorders through topology analysis. Antimetabolites and anti-cancer drug development. The arising prevalence of metabolic diseases calls for a holistic approach for analysis of the underlying nature of abnormalities in cellular functions. Through mathematic representation and topological analysis of cellular metabolism, GEnome scale metabolic Models (GEMs) provide a promising framework for uncovering the mechanistic relationship between genotype and phenotype. GEMs hereby enable uncovering associations between cellular physiology and pathology in a systematic manner. Here we review the current progress on reconstruction of human GEMs and how they have been employed as scaffold for interpreting multi-omics high-throughput data with the objective to identify disease-specific metabolic features. We further discuss recent achievements on how to apply these findings for potential target identification and therapeutic drug development. There are, however, challenges in developing models that correctly describe interactions between cells or tissues, and we therefore discuss how GEMs can be integrated with blood circulation models. Finally, we end the review with proposing some possible future research directions.

@article{Uhlen2015Tissuebased, abstract = { Reconstruction of human generic and condition-specific metabolic models. Identifying metabolic differences through comparing flux distributions using constraint-based modeling. Identifying disease-specific metabolic characters in metabolic disorders through topology analysis. Antimetabolites and anti-cancer drug development. The arising prevalence of metabolic diseases calls for a holistic approach for analysis of the underlying nature of abnormalities in cellular functions. Through mathematic representation and topological analysis of cellular metabolism, {GEnome} scale metabolic Models ({GEMs}) provide a promising framework for uncovering the mechanistic relationship between genotype and phenotype. {GEMs} hereby enable uncovering associations between cellular physiology and pathology in a systematic manner. Here we review the current progress on reconstruction of human {GEMs} and how they have been employed as scaffold for interpreting multi-omics high-throughput data with the objective to identify disease-specific metabolic features. We further discuss recent achievements on how to apply these findings for potential target identification and therapeutic drug development. There are, however, challenges in developing models that correctly describe interactions between cells or tissues, and we therefore discuss how {GEMs} can be integrated with blood circulation models. Finally, we end the review with proposing some possible future research directions. }, added-at = {2018-12-02T16:09:07.000+0100}, author = {Uhl\'{e}n, Mathias and Fagerberg, Linn and Hallstr\"{o}m, Bj\"{o}rn M. and Lindskog, Cecilia and Oksvold, Per and Mardinoglu, Adil and Sivertsson, \AA{}sa and Kampf, Caroline and Sj\"{o}stedt, Evelina and Asplund, Anna and Olsson, IngMarie and Edlund, Karolina and Lundberg, Emma and Navani, Sanjay and Szigyarto, Cristina A. and Odeberg, Jacob and Djureinovic, Dijana and Takanen, Jenny O. and Hober, Sophia and Alm, Tove and Edqvist, Per-Henrik and Berling, Holger and Tegel, Hanna and Mulder, Jan and Rockberg, Johan and Nilsson, Peter and Schwenk, Jochen M. and Hamsten, Marica and von Feilitzen, Kalle and Forsberg, Mattias and Persson, Lukas and Johansson, Fredric and Zwahlen, Martin and von Heijne, Gunnar and Nielsen, Jens and Pont\'{e}n, Fredrik}, biburl = {https://www.bibsonomy.org/bibtex/2f93fc39ba424546daf1578ebea2cafce/karthikraman}, citeulike-article-id = {13498609}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1260419}, citeulike-linkout-1 = {http://www.sciencemag.org/content/347/6220/1260419.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/347/6220/1260419.full.pdf}, citeulike-linkout-3 = {http://www.sciencemag.org/cgi/content/abstract/347/6220/1260419}, citeulike-linkout-4 = {http://view.ncbi.nlm.nih.gov/pubmed/25613900}, citeulike-linkout-5 = {http://www.hubmed.org/display.cgi?uids=25613900}, day = 23, doi = {10.1126/science.1260419}, interhash = {d2b62a655791f38edd6ff4fe96505bff}, intrahash = {f93fc39ba424546daf1578ebea2cafce}, issn = {1095-9203}, journal = {Science}, keywords = {human protein-protein-interactions}, month = jan, number = 6220, pages = 1260419, pmid = {25613900}, posted-at = {2015-01-28 16:32:08}, priority = {2}, publisher = {American Association for the Advancement of Science}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Tissue-based map of the human proteome}, url = {http://dx.doi.org/10.1126/science.1260419}, volume = 347, year = 2015 }