publication . Article . 2011

identifying causal genes and dysregulated pathways in complex diseases

Yoo-Ah Kim; Stefan Wuchty; Teresa M Przytycka;
Open Access
  • Published: 01 Mar 2011 Journal: PLoS Computational Biology, volume 7, page e1001095 (eissn: 1553-7358, Copyright policy)
  • Publisher: Public Library of Science (PLoS)
Abstract
In complex diseases, various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of complex diseases and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in cancer compared to non-tum...
Subjects
free text keywords: Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, Gene regulatory network, Quantitative trait locus, Bioinformatics, Phenotype, Expression quantitative trait loci, Gene dosage, Gene expression profiling, Genomics, Biology, Locus (genetics), Research Article, Computational Biology, Computational Biology/Systems Biology, Biology (General), QH301-705.5
60 references, page 1 of 4

Schadt, EE. Molecular networks as sensors and drivers of common human diseases.. Nature. 2009; 461: 218-223 [OpenAIRE] [PubMed]

Golub, TR, Slonim, DK, Tamayo, P, Huard, C, Gaasenbeek, M. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.. Science. 1999; 286: 531-537 [OpenAIRE] [PubMed]

Perou, CM, Sorlie, T, Eisen, MB, van de Rijn, M, Jeffrey, SS. Molecular portraits of human breast tumours.. Nature. 2000; 406: 747-752 [OpenAIRE] [PubMed]

Ramaswamy, S, Ross, KN, Lander, ES, Golub, TR. A molecular signature of metastasis in primary solid tumors.. Nat Genet. 2003; 33: 49-54 [OpenAIRE] [PubMed]

Nagasaki, K, Miki, Y. Gene expression profiling of breast cancer.. Breast Cancer. 2006; 13: 2-7 [PubMed]

Thompson, M, Lapointe, J, Choi, YL, Ong, DE, Higgins, JP. Identification of candidate prostate cancer genes through comparative expression-profiling of seminal vesicle.. Prostate. 2008; 68: 1248-1256 [OpenAIRE] [PubMed]

Alizadeh, AA, Eisen, MB, Davis, RE, Ma, C, Lossos, IS. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.. Nature. 2000; 403: 503-511 [OpenAIRE] [PubMed]

van 't Veer, LJ, Dai, H, van de Vijver, MJ, He, YD, Hart, AA. Gene expression profiling predicts clinical outcome of breast cancer.. Nature. 2002; 415: 530-536 [PubMed]

Lee, E, Chuang, HY, Kim, JW, Ideker, T, Lee, D. Inferring pathway activity toward precise disease classification.. PLoS Comput Biol. 2008; 4: e1000217 [OpenAIRE] [PubMed]

Keller, A, Backes, C, Gerasch, A, Kaufmann, M, Kohlbacher, O. A novel algorithm for detecting differentially regulated paths based on gene set enrichment analysis.. Bioinformatics. 2009; 25: 2787-2794 [OpenAIRE] [PubMed]

Chuang, HY, Lee, E, Liu, YT, Lee, D, Ideker, T. Network-based classification of breast cancer metastasis.. Mol Syst Biol. 2007; 3: 140 [OpenAIRE] [PubMed]

Doniger, SW, Salomonis, N, Dahlquist, KD, Vranizan, K, Lawlor, SC. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data.. Genome Biol. 2003; 4: R7 [OpenAIRE] [PubMed]

Kohler, S, Bauer, S, Horn, D, Robinson, PN. Walking the interactome for priorization of candidate genes.. Am J Human Genet. 2008; 82: 949-958 [OpenAIRE] [PubMed]

Vanunu, O, Sharan, R. A propagation-based algorithm for inferring gene-disease associations.. 2008; 136: 54-63

Wu, X, Jiang, R, Zhang, MQ, Li, S. Network-based global inference of human disease.. Mol Sys Biol. 2008; 4: 189

60 references, page 1 of 4
Abstract
In complex diseases, various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of complex diseases and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in cancer compared to non-tum...
Subjects
free text keywords: Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, Gene regulatory network, Quantitative trait locus, Bioinformatics, Phenotype, Expression quantitative trait loci, Gene dosage, Gene expression profiling, Genomics, Biology, Locus (genetics), Research Article, Computational Biology, Computational Biology/Systems Biology, Biology (General), QH301-705.5
60 references, page 1 of 4

Schadt, EE. Molecular networks as sensors and drivers of common human diseases.. Nature. 2009; 461: 218-223 [OpenAIRE] [PubMed]

Golub, TR, Slonim, DK, Tamayo, P, Huard, C, Gaasenbeek, M. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.. Science. 1999; 286: 531-537 [OpenAIRE] [PubMed]

Perou, CM, Sorlie, T, Eisen, MB, van de Rijn, M, Jeffrey, SS. Molecular portraits of human breast tumours.. Nature. 2000; 406: 747-752 [OpenAIRE] [PubMed]

Ramaswamy, S, Ross, KN, Lander, ES, Golub, TR. A molecular signature of metastasis in primary solid tumors.. Nat Genet. 2003; 33: 49-54 [OpenAIRE] [PubMed]

Nagasaki, K, Miki, Y. Gene expression profiling of breast cancer.. Breast Cancer. 2006; 13: 2-7 [PubMed]

Thompson, M, Lapointe, J, Choi, YL, Ong, DE, Higgins, JP. Identification of candidate prostate cancer genes through comparative expression-profiling of seminal vesicle.. Prostate. 2008; 68: 1248-1256 [OpenAIRE] [PubMed]

Alizadeh, AA, Eisen, MB, Davis, RE, Ma, C, Lossos, IS. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.. Nature. 2000; 403: 503-511 [OpenAIRE] [PubMed]

van 't Veer, LJ, Dai, H, van de Vijver, MJ, He, YD, Hart, AA. Gene expression profiling predicts clinical outcome of breast cancer.. Nature. 2002; 415: 530-536 [PubMed]

Lee, E, Chuang, HY, Kim, JW, Ideker, T, Lee, D. Inferring pathway activity toward precise disease classification.. PLoS Comput Biol. 2008; 4: e1000217 [OpenAIRE] [PubMed]

Keller, A, Backes, C, Gerasch, A, Kaufmann, M, Kohlbacher, O. A novel algorithm for detecting differentially regulated paths based on gene set enrichment analysis.. Bioinformatics. 2009; 25: 2787-2794 [OpenAIRE] [PubMed]

Chuang, HY, Lee, E, Liu, YT, Lee, D, Ideker, T. Network-based classification of breast cancer metastasis.. Mol Syst Biol. 2007; 3: 140 [OpenAIRE] [PubMed]

Doniger, SW, Salomonis, N, Dahlquist, KD, Vranizan, K, Lawlor, SC. MAPPFinder: using Gene Ontology and GenMAPP to create a global gene-expression profile from microarray data.. Genome Biol. 2003; 4: R7 [OpenAIRE] [PubMed]

Kohler, S, Bauer, S, Horn, D, Robinson, PN. Walking the interactome for priorization of candidate genes.. Am J Human Genet. 2008; 82: 949-958 [OpenAIRE] [PubMed]

Vanunu, O, Sharan, R. A propagation-based algorithm for inferring gene-disease associations.. 2008; 136: 54-63

Wu, X, Jiang, R, Zhang, MQ, Li, S. Network-based global inference of human disease.. Mol Sys Biol. 2008; 4: 189

60 references, page 1 of 4
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publication . Article . 2011

identifying causal genes and dysregulated pathways in complex diseases

Yoo-Ah Kim; Stefan Wuchty; Teresa M Przytycka;