Manolis Kellis (Kamvysselis) manoli@mit.edu |
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Professor, Computer Science, MIT Head, MIT Computational Biology Group Associate Member, Broad Institute of MIT and Harvard Principal Investigator, Computer Science and Artificial Intelligence Lab Stata Center - 32D.524 - 617.253.2419 (contact) Awards: - US Presidential Early Career Award (PECASE) - Alfred P. Sloan Foundation Award - National Science Foundation CAREER Award - AIT Niki Award for Science and Engineering - Technology Review TR35 Top Young Innovators - Ruth and Joel Spira Teaching Award - MIT Sprowls Award for Best PhD Thesis in Computer Science Our group at MIT aims to further our understanding of the human genome by computational integration of large-scale functional and comparative genomics datasets. (1) We use comparative genomics of multiple related species to recognize evolutionary signatures of protein-coding genes, RNA structures, microRNAs, regulatory motifs, and individual regulatory elements. (2) We use combinations of epigenetic modifications to define chromatin states associated with distinct functions, including promoter, enhancer, transcribed, and repressed regions, each with distinct functional properties. (3) We use dynamics of functional elements across many cell types to link regulatory regions to their target genes, predict activators and repressors, and cell type specific regulatory action. (4) We combine these evolutionary, chromatin, and activity signatures to dramatically expand the annotation of the non-coding genome, elucidate the regulatory circuitry of the human and fly genomes, and to revisit previously uncharacterized disease-associated variants, providing mechanistic insights into their likely molecular roles. | ||||
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| Teaching | - | Computational Biology - Personal Genomics - Algorithms - Video lectures - More Teaching | ||
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| Computational Biology - Selected Publications | ||
| Variation and Disease | ||
| Obesity/FTO | - | Adicpocyte Browning underlies FTO Obesity Mechanism |
| Alzheimer's | - | Epigenomics shows Immune Basis of Alzheimer's |
| Roadmap | - | Integrative analysis of 111 reference human epigenomes |
| DiseaseNets | - | Regulatory Circuitry of Disease Variants |
| SubThreshold | - | Genetic + epigenomic discovery of disease loci |
| RiVIERA1 | - | Joint Bayesian Inference of Risk Variants |
| Chrom-GWAS | - | Interpretin variation using cell type specific chromatin state |
| Chrom-var | - | Chromatin state variation across 19 individuals |
| TF-var | - | Trans-regulatory coding variation affecting TF binding |
| DiseaseMapping | - | Interpreting noncoding genetic variation in complex traits and disease |
| HumanSelection | - | Evidence of regulatory turnover in the human genome |
| HaploReg v4 | - | From regions to SNPs, targets, regulators, cell types |
| GTEx | - | Genotype-Expression association across 40 tissues |
| Other | - | ImmVar - Glaucoma - HaploReg v1 |
| Genome Interpretation | ||
| Roadmap | - | Integrative analysis of 111 reference human epigenomes |
| ENCODE | - | Integrative analysis of the human ENCODE project |
| 29 mammals | - | A high-resolution map of evolutionary constraint in the human genome |
| modENCODE | - | Functional elements and regulatory circuits in fly |
| 12flies | - | Evolutionary signatures for systematic genome interpretation in fly |
| Defining Function | - | Relating biochemical, evolutionary, and genetic approaches |
| 4yeasts | - | Gene identification and motif discovery in yeast |
| Other | - | ENCODE 101 - modENCODE - Dog - Neurospora - Platypus |
| Epigenomics and Chromatin regulation | ||
| Chromatin States | - | Combinatorial chromatin patterns for genome annotation |
| ChromSOMs | - | Self organizing maps for epigenomic datasets |
| TF-Chrom | - | Interplay of Chromatin States, TF binding, and Regulatory Motifs |
| ChromHMM | - | Automating chromatin-state discovery and characterization |
| ChromDiff | - | Automating chromatin-state discovery and characterization |
| Smell neurons | - | Epigenetic signature of monoallelic expression in olfactory neurons |
| Fly landscape | - | Chromatin landscape of Drosophila genes and regulatory elements |
| Human Enhancers | - | Tissue-specific enhancers in multiple human cell types |
| Other | - | TFdev - Enhancers - Integration - Nucleosomes - Lamina - ChIP-Seq - Stalling - Embryo - Roadmap - GATA - ChromReg - Fly Insulators |
| Regulatory Networks | ||
| Deconvolution | - | Network Deconvolution to distinguish direct dependencies |
| MetaNets | - | The wisdom of crowds in network inference |
| NetInference | - | Integrative inference of regulatory networks |
| Network Motifs | - | Discovering large motifs using symmetry-breaking conditions |
| SubMAP | - | Aligning large pathways with subnetwork mapping |
| Network Evol | - | Post whole-genome duplication (WGD) network evolution |
| Genome Evolution | ||
| Innovation | - | Three periods of regulatory innovation in vertebrate evolution |
| Duplication | - | Proof and analysis of Whole-Genome Duplication (WGD) in yeast |
| 8candida | - | Evolutionary analysis of 8 candida genomes |
| FishDup | - | Whole-genome duplication in a vertebrate genome |
| Asexual | - | Evolution without sex for an animal species |
| Other | - | FlyEvo - Platypus - Birds - Cholera - Schizo - SeqErrors - Yeast Expr - Arboretum |
| Regulatory Motifs | ||
| Motif Dissection | - | Dissection of regulatory motifs in 2000 human enhancers |
| Motif Discovery | - | Systematic Discovery of motifs in 427 ENCODE experiments |
| Motif selection | - | Regulatory motif instance variation in human and fly |
| Parallel Assays | - | Massively parallel dissection of human enhancers |
| Human Motifs | - | De novo TF/miRNA motif discovery in human |
| Motif Targets | - | Using motifs to infer regulatory networks in fly |
| Fly CisReg | - | A cis-regulatory map of the Drosophila genome |
| Other | - | Long motifs - Yeast Motifs - Motif Pairs - Heart Beat - Position Selection - Yeast Code |
| Long non-coding RNAs and RNA structure | ||
| lincRNAevo | - | lincRNA evolution across 6 mammals and 9 tissues |
| vivoFold | - | RNA folding in vivo, in vitro, and in sillico |
| ncRNAs | - | Computational analysis of non-coding RNAs |
| RNAshape | - | RNA folding with soft constraints integrating experimental evidence |
| lincRNAs | - | Chromatin reveals a new class of long intergenic non-coding RNAs |
| Other | - | lincRNA-KO - RNAchapter - lincRNAneuro - Cancer - Structures - adipogenesis - heart - |
| microRNAs and small ncRNAs | ||
| AntiSense-miRs | - | Discovery of a new class of anti-sense functional microRNAs |
| microRNAs | - | Comparative identification of microRNAs in fly |
| endo-siRNAs | - | Endogenous Small Interfering RNAs |
| miR-targets | - | miRNA target identiification and analysis in Drosophila |
| piRNAs | - | small RNAs repressing retrotransposons in Drosophila |
| Other | - | RiboSwitches - Tasmanian |
| Protein-coding genes | ||
| Readthrough | - | Evidence of abundant stop codon readthrough in animal genomes |
| Overlapping | - | Excess synonymous constraint in 10,000 protein-coding exons in human |
| PhyloCSF | - | Phylogenetic evidence of protein-coding evolutionary signatures |
| Drosophila | - | Revisiting fly genome: new genes and exons, unusual gene structures |
| Signatures | - | Comparing evolutionary and single-species metrics |
| Other | - | shortORFs - Human CCDS - MassSpec - GENCODE |
| Phylogenomics | ||
| DTLrecon | - | Handling multiple optima in dup/loss/transfer reconciliation |
| DLCoalRecon | - | Labeled Coalescent Trees for dup/loss/coal reconciliation |
| DupLossCoal | - | Joint modeling of gene duplication, loss, and incomplete lineage sorting |
| Phylogenomics | - | Bayesian gene-tree phylogenomic reconstruction |
| Phylogeny | - | Learning common gene-tree properties to overcome sparse information |
| Sub-gene | - | Domain-level evolution reveals abundant gene fusion and fission events |
| TreeFix | - | Statistically informed gene-tree error correction using a species tree |
| RangerDTL | - | Duplication, Horizontal Transfer and Loss reconciliation modeling |
| Undergrad/Grad research | ||
| PhD Thesis | - | Received Sprowls award for best PhD thesis in CS |
| Masters Thesis | - | Imagina: Sketch-based image retrieval (applets) |
| RECOMB 2003 | - | Methods in Comparative Genomics |
| Siggraph 98 | - | 3D surface reconstruction (more info) |
| 3D Morphing | - | Polygon-based 3D model morphing |
| ECI Morph | - | Gaussian morphing 2D convex shapes |
| Chars | - | Character Recognition in Curvature Space |
| Other | - | Mood - RoboLogo - Invest - Webbot - Turing - Evolution |
