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研究领域

Applications of genomics, computation, and sequencing technologies to the analysis of transcriptional regulation in development. My laboratory explores how gene regulatory networks that underlie development are encoded in the human genome and we seek to understand their “grammar” using both laboratory and computational methods. We focus on how tissue-specific transcriptional enhancers work, and whether their expression levels and target genes can be predicted from in vivo protein-DNA interactions (as measured using ChIP-seq) and RNA expression (from RNA-seq) of both normal and perturbed differentiation time courses. No reliable computational methods yet exist to link distal enhancers to their target genes (which can be many genes and up to a megabase-pair away in mammals) using sequence, expression or ChIP-data alone. While this identification problem is extremely difficult when considering large and complex genomes linearly, it would be a relatively easy problem if we could capture the three-dimensional interaction of the looping enhancers with their target promoters. We are, therefore, working with techniques that capture long-range chromatin interactions globally, such as ChIA-PET, in developmental time courses in order to integrate these long-range data with ChIP-seq and RNA-seq into testable gene regulatory networks. We are also interested in what fraction of these long-range interactions account for phenotypic variation between individuals and whether they are more likely to be conserved in vertebrates.

近期论文

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Assessment of transcript reconstruction methods for RNA-seq Steijger T, Abril JF, Engström PG, Kokocinski F; The RGASP Consortium, Akerman M, Alioto T, Ambrosini G, Antonarakis SE, Behr J, Bertone P, Bohnert R, Bucher P, Cloonan N, Derrien T, Djebali S, Du J, Dudoit S, Gerstein M, Gingeras TR, Gonzalez D, Grimmond SM, Guigó R, Habegger L, Harrow J, Hubbard TJ, Iseli C, Jean G, Kahles A, Lagarde J, Leng J, Lefebvre G, Lewis S, Mortazavi A, and 26 more authors. Nature Methods, 2013, In press Integrating and mining the chromatin landscape of cell type specificity using Self-Organizing Maps Mortazavi A*$, Pepke S*, Jansen C, Marinov GK, Ernst J, Kellis M, Hardison R, Myers RM, Wold B$ Genome Research, 2013, In press The common ground of genomics and systems biology Conesa A, Mortazavi A BMC Systems Biology, 2013, In press The Draft Genome and Transcriptome of Panagrellus redivivus are shaped by the harsh demands of a free-living lifestyle Srinivasan J, Dilman AR, Macchietto MG, Heikkinen L, Lakso M, Fracchia KM, Antoshechkin I, Mortazavi A, Wong G, Sternberg PW Genetics 2013 Park E, Williams B, Wold B, Mortazavi A (2012) RNA Editing in the ENCODE RNA-seq data. Genome Research.

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