Data Science Approaches for Genome Scale Data Integration & Data Mining
Pathway Bioinformatics and Network Biology
Genomic Architecture and Regulatory Logic
- Systems Immunology: I develop integrative computational approaches to understand the biology of Innate Immunity, Inflammation and Cancer at a Systems level. Specifically, we study Interferons and other innate immune modulators that play important roles in both health and disease. The IFNs mediate their multiple functions by regulating a set of genes known as interferon stimulated genes (ISGs). In order to understand the impact of IFNs in disease we built INTERFEROME, a database of IFN regulated genes and InterferonScape, an integrative web based systems biology application developed to investigate ISG pathways, networks and regulation in different biomedical datasets. We generate our own systems level genomic, transcriptomic, proteomic and epigenetic datasets, and integrating and mining these using statistical & computational methods we are unravelling the complexities of innate immune responses in cancer and other diseases.
- Pathway Bioinformatics and Network Biology: I use computational modelling of biological pathways and networks utilizing high-throughput biomedical data-sets to understand signalling, interaction, regulation, information flow and connectivity at the systems level. I'm investigating pathways and networks in innate immunity, cancer, apoptosis and cellular senescence.
genomics ; signal transduction ; interferons ; chemokines/monokines ; apoptosis ; inflammatory mediators ; proteomics ; data-integration and mining ; computational modelling ; interleukin ; systems biology ; animal models ; cytokines ; bioinformatics ; statistical analysis ; Toll-like receptors ; Toll receptors ; inflammation
- Samarajiwa, S.A., Mangan N.E., Hardy, M.P., Najdovska, M., Dubach, D., Noppert S-J, Owczarek C.M. and Hertzog, P.J "Soluble IFN receptor potentiates in vivo IFN beta signaling and exacerbates TLR4 mediated septic shock" J Immunol.. 2014 April; PMID 24696235
- Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, Andrews D, Mikeska T, Mangan NE, Samarajiwa SA, de Weerd NA, Gould J, Argani P, Möller A, Smyth MJ, Anderson RL, Hertzog PJ, Parker BS. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med. 2012 Jul 22. doi: 10.1038/nm.2830.
- Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S; METABRIC Group; Co-chairs, Caldas C, Aparicio S; Writing committee, Curtis C, Shah SP, Caldas C, Aparicio S; Steering committee, Brenton JD, Ellis I, Huntsman D, Pinder S, Purushotham A, Murphy L, Caldas C, Aparicio S."The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups." Nature 2012 April PMID: 22522925
- Chandra T, Kirschner K, Thuret JY, Pope BD, Ryba T, Newman S, Ahmed K, Samarajiwa SA, Salama R, Carroll T, Stark R, Janky R, Narita M, Xue L, Chicas A, Nũnez S, Janknecht R, Hayashi-Takanaka Y, Wilson MD, Marshall A, Odom DT, Babu MM, Bazett-Jones DP, Tavaré S, Edwards PA, Lowe SW, Kimura H, Gilbert DM, Narita M. Independence of repressive histone marks and chromatin compaction during senescent heterochromatic layer formation. Mol Cell. 2012 Jul 27;47(2):203-14.
- Hertzog P, Forster S, Samarajiwa S. "Systems biology of interferon responses." J Interferon Cytokine Res. 2011 Jan; 31(1):5-11. PMID: 21226606
- Narita M, Young AR, Arakawa S, Samarajiwa SA, Nakashima T, Yoshida S, Hong S, Berry LS, Reichelt S, Ferreira M, Tavaré S, Inoki K, Shimizu S, Narita M. Spatial coupling of mTOR and autophagy augments secretory phenotypes. Science. 2011 May 20;332(6032):966-70.
- Harman AN, Lai J, Turville S, Samarajiwa S, Gray L, Marsden V, Mercier S, Jones K, Nasr N, Rustagi A, Cumming H, Donaghy H, Mak J, Gale M Jr, Churchill M, Hertzog P and Cunningham AL. "HIV infection of dendritic cells subverts the interferon induction pathway and inhibits Type 1 interferon production" Blood. 2011 May PMID: 21411754
- Samarajiwa SA, Forster S, Auchettl K, Hertzog PJ. INTERFEROME: the database of interferon regulated genes. Nucleic Acids Res. 2009 Jan;37(Database issue):D852-7.
- de Weerd NA, Samarajiwa SA, Hertzog PJ. Type I interferon receptors: biochemistry and biological functions. J Biol Chem. 2007 Jul 13;282(28):20053-7.
- Shamith Samarajiwa, William Wilson, Paul Hertzog 2006 “Type I Interferons: Genetics and Structure” in “The Interferons: characterization and application” Ed. Anthony Meager, Wiley-VCH.