Systems Biology of Disease

 

We provide a very brief overview of our current work in this area that broadly covers three areas.  We typically focus on network based approaches to produce highly predictive systems that either predict the function of genes, their regulation or biological networks or modules associated with disease. These serve as novel biomarkers or drug targets.

We also somewhat specialize in integration of networks with molecular data.  We sometimes test our ideas on “simple organisms” such as bacteria, Yeast, worm, or mouse before expanding to analysis of human data.

 

Diabetes

Cancer

Aging

 

Selected publications:

  1. One for all and all for One: Improving replication of genetic studies through network diffusion. Lancour D, Naj A, Mayeux R, Haines JL, Pericak-Vance MA, Schellenberg GD, Crovella M, Farrer LA, Kasif S. PLoS Genet. 2018 Apr 23;14(4):e1007306. doi: 10.1371/journal.pgen.1007306. eCollection 2018 Apr. PMID: 29684019
  2. Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes. Ramirez AK, Lynes MD, Shamsi F, Xue R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM. Cell Rep. 2017 Dec 12;21(11):3040-3048. doi: 10.1016/j.celrep.2017.11.065. PMID: 29241534 (Best Graduate Student Paper award to Alfred Ramirez).
  3. Unexpected Properties of Short Genomic Tandem Repeats I Glotova, M Molla, AL Delcher, S Kasif bioRxiv, 165308
  4. Not All Experimental Questions Are Created Equal: Accelerating Biological Data to Knowledge Transformation (BD2K) via Science Informatics, Active Learning and Artificial Intelligence, Kasif,S, Letovsky S, Roberts, RJ,  Steffen,M,  bioRxiv, 2017 (**Can computers help biologists come up with high impact biology questions**)
  5. Unexpected Properties of Short Genomic Tandem Repeats. ,Glotova, I, Molla, M, Delcher, AL, Kasif, S,  bioRxiv, 165308, (2017)
  6. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism. Lerin C, Goldfine AB, Boes T, Liu M, Kasif S, Dreyfuss JM, De Sousa-Coelho AL, Daher G, Manoli I, Sysol JR, Isganaitis E, Jessen N, Goodyear LJ, Beebe K, Gall W, Venditti CP, Patti ME. Mol Metab. 2016 Aug 6;5(10):926-36. doi: 10.1016/j.molmet.2016.08.001. eCollection 2016 Oct. PMID: 27689005

  7. COMBREX-DB: an experiment centered database of protein function: knowledge, predictions and knowledge gaps. Chang YC, Hu Z, Rachlin J, Anton BP, Kasif S, Roberts RJ, Steffen M.Nucleic Acids Res. 2015 Dec 3. pii: gkv1324. [Epub ahead of print] PMID: 26635392. (**first database that allows searching of knowledge gaps – SEARCHING THE SPACE THAT WE DON’T KNOW **)

  8. Metabolic modeling of muscle metabolism identifies key reactions linked to insulin resistance phenotypes. Nogiec C, Burkart A, Dreyfuss JM, Lerin C, Kasif S, Patti ME. Mol Metab. 2015 Jan 2;4(3):151-63. doi: 10.1016/j.molmet.2014.12.012. eCollection 2015 Mar. PMID: 25737951 (COVER). (** first FBA modeling modeling of insulin resistance with experimental validations **) 

  9. Identification of rare germline copy number variations over-represented in five human cancer types. Park RW, Kim TM, Kasif S, Park PJ. Mol Cancer. 2015 Feb 3;14(1):25. [Epub ahead of print] PMID: 25644941
  10. Objective: Biochemical Function. Anton BP, Kasif S, Roberts RJ, Steffen M. Nature Frontiers in Genetics, 2014
  11. Hypermutable DNA chronicles the evolution of human colon cancer. Naxerova K, Brachtel E, Salk JJ, Seese AM, Power K, Abbasi B, Snuderl M, Chiang, S, Kasif S, Jain RK. Proc Natl Acad Sci U S A. 2014 PMID: 24753616
  14. Reconstructing and reprogramming the developmental hierarchy of glioblastoma, Mario L. Suvà*, Esther Rheinbay* et al, Cell, 2014.
  15. An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Rheinbay E, Suvà ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE. Cell Reports. 2013 May 30;3(5):1567-79.  2013.04.021. Epub 2013 May 23. PMID: 23707066
  16. Systems biology characterization of engineered tissues. Rajagopalan P, Kasif S, Murali TM. Annu Rev Biomed Eng. 2013;15:55-70. doi: 10.1146/annurev-bioeng-071811-150120. PMID: 23862675
  17. To supplement or not to supplement: a metabolic network framework for human nutritional supplements. Nogiec CD, Kasif S. PLoS One. 2013;8(8):e68751. doi: 10.1371/journal.pone.0068751. PMID: 23967053
  18. Deep sequencing of the oral microbiome reveals s signatures of periodontal disease, Bo Liu1,2*, Lina Faller3*, Niels Klitgord3*, Varun Mazumdar3*, Mohammad Ghodsi1,2,Daniel D. Sommer1, Theodore R. Gibbons1,4, Todd J. Treangen1,10, Yi-Chien Chang3,Shan Li5, O. Colin Stine5, Hatice Hasturk8, Simon Kasif3,7,9, Daniel Segrè3,6,7#,  Mihai Pop1,2,4#, Salomon Amar3,8#,, PLOS One, 2012
  19. Network Signatures of Insulin Resistance and Life Span, M. Liu, M. Mori, IS. Kohane, ME Patti, A. Goldfine, CR Kahn, S. Kasif, in preparation.
  20. Chris Nogiec, Allison Burkhart, Jonathan Dreyfuss, Simon Kasif* and ME Patti*, Metabolic Analysis of Insulin Resistance, in revision (contributed equally authors), in review.
  21. Towards a Personal Repeatome: A Genome-Wide Survey of Length Variation in Short Tandem Repeats in Human Gene Transcripts, in preparation.
  22. A Critical Assessment of Genomic and Clinical Breast Cancer Biomarkers. Chang-Jiun Wu, Tianxi Cai, Zoltan Szallasi, Kamila Naxerova, Martin Steffen, L.J. Wei, Isaac S. Kohane*, Simon Kasif*, co-corresponding authors, in revision.
  23. Integrative Pheno-genomic module discovery with application to breast cancer, Chang-Jiun Wu, Tianxi Cai, Isaac S. Kohane*, Simon Kasif*, in revision.
  24. A Systems Biology Approach Links Inflammation to the Predisposition to Metabolic Diseases in Mouse Strains, Marcelo Mori*, Manway Liu*, Simon Kasif, Ron Kahn, Diabetes 2010.
  25. Transcriptome Analysis Reveals Parallel Dysregulation of Oxidative Metabolism and Inflammation in Muscle and Adipose Tissue With Progression of Insulin Resistance in Humans, Mary-Elizabeth Patti, Manway Liu, Wanzhu Jin, Carles Lerin, Jonathan Dreyfuss, Martha Vokes, Joshua Schroeder, Elizabeth Tatro, Peter Park, Isaac Kohane, Igor Leykin, Simon Kasif, and Allison Goldfine, in preparation.
  26. Drug Response Phosphorylation Signatures of Lung Cancer, Chang-Jiun Wu, Martin Steffen, Simon Kasif in preparation.
  27. A Predictive phosphorylation signature of lung cancer. Chang-Jiun Wu, Tianxi Cai, Klarisa Rikova, David Merberg, Simon Kasif,* Martin Steffen*, co-corresponding authors,  PLoS ONE, Nov 2009.
  28. Triplet repeat length bias and variation in the human transcriptome,  Molla M*, Delcher A*, Cantor CR, Kasif S, Proc. of National Academy of Sciences, Oct. 2009, PMID: 19805156
  29. Integration of heterogeneous expression data sets extends the role of the retinol pathway in diabetes and insulin resistance. Park PJ, Kong SW, Tebaldi T, Lai WR, Kasif S, Kohane IS. Bioinformatics. 2009 Dec 1;25(23):3121-7. Epub 2009 Sep 28.PMID: 19786482
  30. Biological process linkage networks. Dotan-Cohen D, Letovsky S, Melkman AA, Kasif S. PLoS ONE. 2009;4(4):e5313. Epub 2009 Apr 23. PMID 19390589
  31. Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice. Isganaitis E, Jimenez-Chillaron J, Woo M, Chow A, DeCoste J, Vokes M, Liu M, Kasif S, Zavacki AM, Leshan RL, Myers MG, Patti ME. Diabetes. 2009 May;58(5):1192-200. Epub 2009 Feb 10. PMID: 19208909
  32. Quantitative analysis of single nucleotide polymorphisms within copy number variation. Lee S, Kasif S, Weng Z, Cantor CR. PLoS ONE. 2008;3(12):e3906. Epub 2008 Dec 18. PMID: 19093001
  33. Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains. Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE. PLoS Genet. 2008 Oct;4(10):e1000242. Epub 2008 Oct 31. PMID: 18974828
  34. Analysis of gene expression in a developmental context emphasizes distinct biological leitmotifs in human cancers. Naxerova K, Bult CJ, Peaston A, Fancher K, Knowles BB, Kasif S, Kohane IS. Genome Biol. 2008;9(7):R108. Epub 2008 Jul 8. PMID: 18611264
  35. Context specific protein function prediction. Nariai N, Kasif S. Genome Inform. 2007; 18:173-82. PMID: 18546485
  36. Tullai JW, Schaffer ME, Mullenbrock S, Sholder G, Kasif S, Cooper GM. Immediate-early and delayed primary response genes are distinct in function and genomic architecture, J Biol Chem. 2007 Jun 15;
  37. Liu M, Liberzon A, Kong SW, Lai WR, Park PJ, Kohane IS, Kasif S. Network-based analysis of affected biological processes in type 2 diabetes models. PLoS Genet. 2007 Jun 15;3(6):e96. PMID:17571924
  38. Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, Kasif S, Collins JJ, Gardner TS. Large-Scale Mapping and Validation of Escherichia coli Transcriptional Regulation from a Compendium of Expression Profiles., PLoS Biol. 2007 Jan 9;5(1):e8 PMID: 17214507
  39. Murali TM, Wu CJ, Kasif S. The art of gene function prediction. Nature Biotechnology. 2006 Dec;24(12):1474-5. PMID: 17160037
  40. Rachlin J, Cohen DD, Cantor C, Kasif S. Biological context networks: a mosaic view of the interactome. Nature/Embo. Mol Syst Biol. 2006;2:66. Epub 2006 Nov 28. PMID: 17130868
  41. Lee S, Kohane I, Kasif S. Genes involved in complex adaptive processes tend to have highly conserved upstream regions in mammalian genomes. BMC Genomics. 2005 Nov 27;6:168. PMID: 16309559
  42. Tullai JW, Schaffer ME, Mullenbrock S, Kasif S, Cooper GM. Identification of transcription factor binding sites upstream of human genes regulated by the phosphatidylinositol 3-kinase and MEK/ERK signaling pathways. J Biol Chem. 2004 May 7;279(19):20167-77. Epub 2004 Feb 9. PMID: 14769801
  43. Su Y, Murali TM, Pavlovic V, Schaffer M, Kasif S. RankGene: identification of diagnostic genes based on expression data. Bioinformatics. 2003 Aug 12;19(12):1578-9. PMID: 12912841

 

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