>RKarnik |
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− | The ultimate goal of our research is to understand how genomic DNA sequence specifies gene regulation. We are currently focused on 1) developing computational tools to identify functional regulatory elements in non-coding DNA, and 2) experimentally testing and characterizing how these elements function.
| + | '''[http://www.hopkinsmedicine.org/news/media/releases/vulnerabilities_in_genomes_dimmer_switches_should_shed_light_on_hundreds_of_complex_diseases Nature Genetics paper on impact of regulatory variants]''' |
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− | In our computational work, we are using microarray gene expression data, genome-wide location analysis, and whole-genome DNA sequence to systematically identify DNA functional elements and infer combinatorial regulatory logic. We use pattern recognition algorithms to identify over-represented and phylogenetically conserved DNA sequence elements (or putative transcription factor binding sites). We then use a probabilistic Bayesian network to find the most likely functional constraints on the position, spacing, orientation, and combinations of these DNA sequence elements. This methodology has generated a large set of high confidence predictions for regulatory interactions, and is in principle applicable to any organism with microarray and genome sequence data.
| + | '''[http://www.newsweek.com/humans-and-mice-are-both-more-similar-and-different-previously-thought-285635 Newsweek article on Mouse ENCODE paper]''' |
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− | In our experimental work, we are testing these computational predictions by rapid generation of transgenic GFP reporter strains in C. elegans via microparticle bombardment. C. elegans is an attractive model system for several reasons:
| + | '''[http://www.hopkinsmedicine.org/news/media/releases/scientists_map_mouse_genomes_mission_control_centers Mouse ENCODE Consortium paper in Nature]''' |
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− | * Relevance to human disease: About 60% of C. elegans genes have a human homologue (Harris et al., NAR 2004); and 80% of genes implicated in human cancer have a worm homologue (Futreal et al., Nat Rev Cancer 2004; Poulin et al, Oncogene 2004).
| + | '''[http://www.bme.jhu.edu/news-events/news-highlights.php?id=412 Beer Lab awarded NIH grant for regulatory contributions to disease. ]''' |
− | * The high quality of the genome sequence data and microarray tools.
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− | * Rapid and effective transformation techniques and GFP reporter assays.
| + | '''[http://www.bme.jhu.edu/news-events/news-highlights.php?id=360 kmer-SVM Genome Research paper voted Top 10 in Regulatory Genomics.] ''' |
− | * Availablity of bacterial feeding library for genome wide RNAi screens to further characterize regulatory interactions.
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− | * Relative ease and cost of strain maintenance.
| + | '''[http://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/news_events/Announcements/2013_04_YID.html Dongwon Lee awarded Young Investigator Day Award.] ''' |