Research Topics
Genomes and Genes | Manolis KellisSummaryAffiliation: Massachusetts Institute of Technology Country: USA Publications
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Publications
Position specific variation in the rate of evolution in transcription factor binding sitesAlan M Moses
Graduate Group in Biophysics, University of California, Berkeley, CA 94720, USA
BMC Evol Biol 3:19. 2003..Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution...
Sequencing and comparison of yeast species to identify genes and regulatory elementsManolis Kellis
Whitehead MIT Center for Genome Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 423:241-54. 2003..We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human...
Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiaeManolis Kellis
The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02138, USA
Nature 428:617-24. 2004..Strikingly, 95% of cases of accelerated evolution involve only one member of a gene pair, providing strong support for a specific model of evolution, and allowing us to distinguish ancestral and derived functions...
The changing face of genomicsManolis Kellis
The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02138, USA
Genome Biol 5:324. 2004
Discovery of functional elements in 12 Drosophila genomes using evolutionary signaturesAlexander Stark
The Broad Institute, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02140, USA
Nature 450:219-32. 2007..We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies...
A single Hox locus in Drosophila produces functional microRNAs from opposite DNA strandsAlexander Stark
Broad Institute of Massachussetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02141, USA
Genes Dev 22:8-13. 2008..We also report sense/antisense miRNAs in mouse and find antisense transcripts close to many miRNAs in both flies and mammals, suggesting that additional sense/antisense pairs exist...
A high-resolution map of human evolutionary constraint using 29 mammalsKerstin Lindblad-Toh
Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 478:476-82. 2011..Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease...
Identification of functional elements and regulatory circuits by Drosophila modENCODESushmita Roy
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology MIT, Cambridge, MA 02139, USA
Science 330:1787-97. 2010..Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation...
Distinguishing protein-coding and noncoding genes in the human genomeMichele Clamp
Broad Institute of Massachusetts Institute of Technology and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 104:19428-33. 2007..It also provides a principled methodology for evaluating future proposed additions to the human gene catalog. Finally, the results indicate that there has been relatively little true innovation in mammalian protein-coding genes...
Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sitesXiaohui Xie
Broad Institute of MIT and Harvard, Massachusetts Institute of Technology and Harvard Medical School, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 104:7145-50. 2007..These sites may thus partition the human genome into domains of expression...
Accurate gene-tree reconstruction by learning gene- and species-specific substitution rates across multiple complete genomesMatthew D Rasmussen
MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts 02139, USA
Genome Res 17:1932-42. 2007....
Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cellsOren Ram
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
Cell 147:1628-39. 2011..Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function...
RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryoJulia Zeitlinger
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nat Genet 39:1512-6. 2007..We propose that Pol II stalling facilitates rapid temporal and spatial changes in gene activity during development...
Systematic discovery and characterization of fly microRNAs using 12 Drosophila genomesAlexander Stark
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
Genome Res 17:1865-79. 2007..For mir-10 in particular, both arms show abundant processing, and both show highly conserved target sites in Hox genes, suggesting a possible cooperation of the two arms, and their role as a master Hox regulator...
Reliable prediction of regulator targets using 12 Drosophila genomesPouya Kheradpour
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genome Res 17:1919-31. 2007..The resulting regulatory network suggests significant redundancy between pre- and post-transcriptional regulation of gene expression...
PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regionsMichael F Lin
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street 32 D510, Cambridge, MA 02139, USA
Bioinformatics 27:i275-82. 2011..AVAILABILITY AND IMPLEMENTATION: The Objective Caml source code and executables for GNU/Linux and Mac OS X are freely available at http://compbio.mit.edu/PhyloCSF CONTACT: mlin@mit.edu; manoli@mit.edu...
Evolution, biogenesis, expression, and target predictions of a substantially expanded set of Drosophila microRNAsJ Graham Ruby
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
Genome Res 17:1850-64. 2007....
Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomesMichael F Lin
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA
Genome Res 17:1823-36. 2007..These results affect >10% of annotated fly genes and demonstrate the power of comparative genomics to enhance our understanding of genome organization, even in a model organism as intensively studied as Drosophila melanogaster...
Mapping and analysis of chromatin state dynamics in nine human cell typesJason Ernst
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
Nature 473:43-9. 2011..Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease...
Locating protein-coding sequences under selection for additional, overlapping functions in 29 mammalian genomesMichael F Lin
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genome Res 21:1916-28. 2011..Our results show that overlapping functional elements are common in mammalian genes, despite the vast genomic landscape...
The evolutionary dynamics of the Saccharomyces cerevisiae protein interaction network after duplicationAviva Presser
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
Proc Natl Acad Sci U S A 105:950-4. 2008..This could suggest a structural difference between the modern and ancestral networks, preferential addition or retention of interactions between ohnologs, or selective pressure to preserve duplicates of self-interacting proteins...
Methods in comparative genomics: genome correspondence, gene identification and regulatory motif discoveryManolis Kellis
Whitehead Institute Center for Genome Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
J Comput Biol 11:319-55. 2004..Our methods are validated by the extensive experimental knowledge in yeast and will be invaluable in the study of complex genomes like that of the human...
Transcriptional regulatory code of a eukaryotic genomeChristopher T Harbison
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 431:99-104. 2004..We find that environment-specific use of regulatory elements predicts mechanistic models for the function of a large population of yeast's transcriptional regulators...
Genome sequence, comparative analysis and haplotype structure of the domestic dogKerstin Lindblad-Toh
Broad Institute of Harvard and MIT, 320 Charles Street, Cambridge, Massachusetts 02141, USA
Nature 438:803-19. 2005..The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health...
Discovery and characterization of chromatin states for systematic annotation of the human genomeJason Ernst
MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, Massachusetts, USA
Nat Biotechnol 28:817-25. 2010..This approach provides a complementary functional annotation of the human genome that reveals the genome-wide locations of diverse classes of epigenetic function...
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammalsMitchell Guttman
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
Nature 458:223-7. 2009..Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes...
Sequences to systemsManolis Kellis
Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Genome Biol 11:303. 2010..A report of the seventh annual meeting on Systems Biology: Global Regulation of Gene Expression, 23-27 March 2010, Cold Spring Harbor, USA...
Evidence of abundant stop codon readthrough in Drosophila and other metazoaIrwin Jungreis
MIT Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Genome Res 21:2096-113. 2011....
Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammalsXiaohui Xie
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
Nature 434:338-45. 2005..The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available...
Large-scale discovery and validation of functional elements in the human genomeBradley E Bernstein
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Genome Biol 6:312. 2005..A report on the genomics workshop 'Identification of Functional Elements in Mammalian Genomes', Cold Spring Harbor, New York, 11-13 November 2004...
Whole-genome ChIP-chip analysis of Dorsal, Twist, and Snail suggests integration of diverse patterning processes in the Drosophila embryoJulia Zeitlinger
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Genes Dev 21:385-90. 2007..Thus, the ChIP-chip data uncover a much larger than expected regulatory network, which integrates diverse patterning processes during development...
The NIH Roadmap Epigenomics Mapping ConsortiumBradley E Bernstein
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
Nat Biotechnol 28:1045-8. 2010....
HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variantsLucas D Ward
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology and The Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA
Nucleic Acids Res 40:D930-4. 2012..HaploReg will be useful to researchers developing mechanistic hypotheses of the impact of non-coding variants on clinical phenotypes and normal variation. The HaploReg database is available at http://compbio.mit.edu/HaploReg...
Performance and scalability of discriminative metrics for comparative gene identification in 12 Drosophila genomesMichael F Lin
Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, United States of America
PLoS Comput Biol 4:e1000067. 2008..Our results have implications for comparative genomics analyses in any species, including the human...
Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeastsDerek Y Chiang
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Genome Biol 4:R43. 2003..Our work suggests that positional information, especially the relative spacing between transcription factor binding sites, may represent a common organizing principle of transcription control regions...
Discrete small RNA-generating loci as master regulators of transposon activity in DrosophilaJulius Brennecke
Cold Spring Harbor Laboratory, Watson School of Biological Sciences and Howard Hughes Medical Institute, Cold Spring Harbor, NY 11724, USA
Cell 128:1089-103. 2007..Thus, sense piRNAs, formed following cleavage of transposon mRNAs may enhance production of antisense piRNAs, complementary to active elements, by directing cleavage of transcripts from master control loci...
Evolution of genes and genomes on the Drosophila phylogenyAndrew G Clark
Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA
Nature 450:203-18. 2007..These may prove to underlie differences in the ecology and behaviour of these diverse species...
Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotypeOlivier Jaillon
UMR 8030 Genoscope, , , 91057 Evry Cedex, France
Nature 431:946-57. 2004....
Genome analysis of the platypus reveals unique signatures of evolutionWesley C Warren
Genome Sequencing Center, Washington University School of Medicine, Campus Box 8501, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA
Nature 453:175-83. 2008..Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation...
An endogenous small interfering RNA pathway in DrosophilaBenjamin Czech
Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA
Nature 453:798-802. 2008..These observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles...
Conservation of small RNA pathways in platypusElizabeth P Murchison
Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
Genome Res 18:995-1004. 2008..Platypus and echidna testes contain a robust Piwi-interacting (piRNA) system, which appears to be participating in ongoing transposon defense...
Research Grants
- Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsManolis Kellis; Fiscal Year: 2007..A global map of regulatory motifs constitutes a necessary knowledge infrastructure towards a comprehensive understanding of regulation, development, and disease. ..
- Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsManolis Kellis; Fiscal Year: 2009..A global map of regulatory motifs constitutes a necessary knowledge infrastructure towards a comprehensive understanding of regulation, development, and disease. ..
- Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsManolis Kellis; Fiscal Year: 2010..A global map of regulatory motifs constitutes a necessary knowledge infrastructure towards a comprehensive understanding of regulation, development, and disease. ..
- Regulatory Morif Discovery in the Human Genome Using Comparative GenomicsManolis Kellis; Fiscal Year: 2010..A global map of regulatory motifs constitutes a necessary knowledge infrastructure towards a comprehensive understanding of regulation, development, and disease. ..
