Research

Genome-scale experimental platforms provide vast amounts of data with the potential to dramatically improve our understanding of biology and pave the way to new therapies for human diseases. The challenge now is developing the right conceptual and mathematical frameworks to process and interpret these data, and ultimately transform it into knowledge about biological systems.

The primary goal of my research is to provide actionable data-driven models for use in cancer genomics and drug development. The main interest lies in network-based methods that extend across multiple data dimensions: genome, transcriptome, proteome, metabolome; and multiple biological scales: from single genes and proteins, to complexes and pathways, to entire cells, tissues and organs. My recent work includes algorithms for mapping dynamic changes in networks during development and in response to disease and stress conditions, robust methods for biomarker identification, and probabilistic methods for comparing biological networks across species.

Most recently I developed a computational method for constructing network-based ontologies of gene function. Ontologies are essential in many domains, capturing knowledge as a hierarchy of concepts and their interrelationships. Most ontologies, including those in biology, are typically developed through manual expert curation. In our work, we found that the vast amounts of genomic data now available can be transformed to automatically assemble on ontology of gene function that rivals manually constructed ontologies in coverage and power. Our network-extracted ontology (NeXO) provides a new resource for systems and synthetic biology - i.e. a data-driven multiscale catalog of cellular machinery, from genes to complexes, to pathways and higher-order processes. It also provides a way to systematically update manually constructed ontologies with new terms and relationships derived from high-throughput data (see article and commentary in Nature Biotechnology). You can access the NeXO ontology using Cytoscape or an OBO file browser such as OBO-Edit (see here). NeXO is now also available online:www.nexontology.org.


Journal articles

(*) corresponding author
  • Bilal E, Dutkowski J (co-first author), Guinney J, Jang IS, Logsdon BA, Pandey G, Sauerwine BA, Shimoni Y, et al. Improving breast cancer survival analysis through competition-based multidimensional modeling. PLoS Computational Biology, In press.
  • Dutkowski J*, Kramer M, Surma, MA, Balakrishnan R, Cherry JM, Krogan NJ, Ideker T* . A gene ontology inferred from molecular networks. Nature Biotechnology. Advance online publication December 16, 2012 (doi:10.1038/nbt.2463). Pubmed Journal
  • Dutkowski J*, Ideker T*. Protein networks as logic functions in development and cancer. PLoS Computational Biology. 2011. 7(9): e1002180. Pubmed Journal
  • Ideker T*, Dutkowski J, Hood L. Boosting signal-to-noise in complex biology: prior knowledge is power, Cell. 2011. 144(6):860-863. PubMed Journal
  • Mercer EM, Lin YC, Benner C, Jhunjhunwala S, Dutkowski J, Flores M, Sigvardsson M, Ideker T, Glass CK, Murre C*. Multilineage priming of enhancer repertoires precedes commitment to the B and myeloid cell lineages in hematopoietic progenitors, Immunity. 2011. 35(3):413-25. PubMed Journal
  • Bandyopadhyay S, Mehta M, Kuo D, Sung M, Chuang R, Jaehnig E, Bodenmiller B, Licon K, Copeland W, Shales M, Fiedler D, Dutkowski J, Guénolé A, van Attikum, H, Shokat K, Kolodner RD, Huh W, Aebersold R, Keogh MC, Krogan NJ, Ideker T*. Rewiring of genetic networks in response to DNA damage. Science. 2010; 330:1385-1389. PubMed Journal
  • Lin YC, Jhunjhunwala S, Benner C, Heinz S, Welinder E, Mansson R, Sigvardsson M, Hagman J, Espinoza CA, Dutkowski J, Ideker T, Glass CK, Murre C*. A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate. Nat Immunol. 2010 Jul;11(7):635-43. PubMed Journal
  • Woźniak M, Tiuryn J, Dutkowski J*. MODEVO: exploring modularity and evolution of protein interaction networks. Bioinformatics. 2010; 26(14):1790-1. PubMed Journal
  • Dutkowski J*, Tiuryn J. Phylogeny-guided interaction mapping in seven eukaryotes. BMC Bioinformatics. 2009;10:393. PubMed Journal
  • Gambin A*, Szczurek E, Dutkowski J, Bakun M, Dadlez M. Classification of peptide mass fingerprint data by novel no-regret boosting method. Comput Biol Med. 39(5):460-73, 2009. PubMed Journal
  • Dutkowski J*, Tiuryn J. Identification of functional modules from conserved ancestral protein-protein interactions, Bioinformatics 2007 23: i149-i158, proceedings of ISMB/ECCB 2007. PubMed Journal
  • Dutkowski J*, Gambin A*. On consensus biomarker selection, BMC Bioinformatics 2007, 8(Suppl 5):S5. PubMed Journal
  • Gambin A*, Dutkowski J , Karczmarski J, Kluge B, Kowalczyk K, Ostrowski J, Poznański J, Tiuryn J, Bakun M, Dadlez M. Automated reduction and interpretation of multidimensional mass spectra for analysis of complex peptide mixtures, International Journal of Mass Spectrometry, 2007, 260:20-30. Journal

Recent conference talks

RECOMB SB-Day 1. 1800 Janusz Dutkowski. from bocemtium on Vimeo.

  • Turning networks into ontologies of gene function, talk at RECOMB Systems Biology, San Francisco 2012.
  • A network-based gene ontology for yeast, talk at the Yeast Genetics Meeting, Princeton 2012.
  • From networks to ontologies of gene function, talks at ISMB Network SIG and Ontologies SIG meeting, Long Beach 2012.
  • Protein networks as logic functions in development and cancer, talk at RECOMB Systems Biology, Barcelona 2011.
  • Inferring combinatorial transcriptional regulation using protein networks, talk at the Integrative Network Biology and Cancer 2.0 meeting, ICR London 2011.
  • Protein networks as logic functions underlying disease, talk at Systems Biology: Networks 2011 Meeting, Cold Spring Harbor.
  • Phylogeny-guided interaction mapping, talk at Systems Biology: Networks 2009 Meeting, Cold Spring Harbor.
  • Identification of functional modules from conserved ancestral protein-protein interactions, talk at ISMB/ECCB 2007, Vienna.

Other activities

  • Academic Coordinator for San Diego Center for Sytems Biology.
  • Reviewer for Science, Nature Methods, PLoS Computational Biology, Bioinformatics, Journal of Compuational Biology, ISMB, RECOMB