Manolis Kellis (Kamvysselis)


FTO obesity variant dissection

Roadmap Epigenomics

Immune basis of Alzheimer's Disease

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Manolis Kellis, Ph.D.
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)

- 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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Funding -
NIH.R01 - Motif discovery in human
NSF.CAREER - Comparative genomics
NIH.RC2 - modENCODE data integration
NIH.RC1 - Epigenome integrative analysis
ENCODE - Chromatin marks in human
EDACC - ENCODE data integration
cisreg - TFs and Chromatin in Fly
NIH.RC1 - smallRNAs and Chromatin
GENCODE - Gene identification in human
NSF.TreeOfLife - Phylogenomics
My pages - Twitter - LinkedIn - CSAIL - EECS - Broad - CSBi - Facebook Group -
 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
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
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