Manolis Kellis

Manolis Kellis
Manolis Kellis at the American Society of Human Genetics (ASHG) meeting in Orlando Florida on October 19, 2017
Born Manolis Kamvysellis
Greek: Μανώλης Καμβυσέλλης
(1977-03-13) March 13, 1977
Athens, Greece
Alma mater Massachusetts Institute of Technology (PhD)
Known for ENCODE
Awards
Scientific career
Fields
Thesis Computational Comparative Genomics: Genes, Regulation, Evolution. (2003)
Doctoral advisor
Website kellislab.com

Manolis Kellis (born 1977, Greek: Μανώλης Καμβυσέλλης) is a professor of Computer Science at the Massachusetts Institute of Technology (MIT) in the area of Computational Biology and a member of the Broad Institute of MIT and Harvard.[3] He is the head of the Computational Biology Group at MIT[4] and is a Principal Investigator in the Computer Science and Artificial Intelligence Lab (CSAIL) at MIT.[5]

Kellis is known for his contributions to genomics, human genetics, epigenomics, gene regulation, and genome evolution. He co-led the NIH Roadmap Epigenomics Project[6] effort to create a comprehensive map of the human epigenome,[7][8][9] the comparative analysis of 29 mammals to create a comprehensive map of conserved elements in the human genome,[10][11] the ENCODE, GENCODE, and modENCODE projects to characterize the genes, non-coding elements, and circuits of the human genome and model organisms.[12][13][14] A major focus of his work is understanding the effects of genetic variations on human disease,[15] with contributions to obesity,[16][17][18] diabetes,[19] Alzheimer's disease,[20][21][22] schizophrenia,[23] and cancer.[24]

Education and early career

Kellis was born in Greece, moved with his family to France when he was 12, and came to the U.S. in 1993.[25] He obtained his PhD from MIT, where he worked with Eric Lander, founding director of the Broad Institute, and Bonnie Berger, professor at MIT[26] and received the Sprowls award for the best doctorate thesis in Computer Science,[27] and the first Paris Kanellakis graduate fellowship.[28] Prior to computational biology, he worked on artificial intelligence, sketch and image recognition, robotics, and computational geometry, at MIT and at the Xerox Palo Alto Research Center.[26]

Research and career

As of July 2018, Manolis Kellis has authored 187 journal publications[29] that have been cited 68,380 times.[1] He has helped direct several large-scale genomics projects, including the Roadmap Epigenomics project,[30][7] the Encyclopedia of DNA Elements (ENCODE) project,[31] the Genotype Tissue-Expression (GTEx) project.[15]

Comparative genomics

Kellis started comparing the genomes of yeast species as an MIT graduate student. As part of this work, which was published in Nature in 2003,[32] he developed computational methods to pinpoint patterns of similarity and difference between closely related genomes. The goal was to develop methods for understanding genomes with a view to apply them to the human genome.

He turned from yeast to flies and ultimately to mammals, comparing multiple species to explore genes, their control elements, and their deregulation in human disease.[33] Kellis led several comparative genomics projects in human,[33] mammals,[34][10] flies,[35][36] and yeast.[37]

Epigenomics

Kellis co-led the NIH government-funded project to catalogue the human epigenome. He said during an interview with MIT Technology Review[33] “If the genome is the book of life, the epigenome is the complete set of annotations and bookmarks.”[33] His lab now uses this map to further the understanding of fundamental processes and disease in humans.

Obesity

Kellis and colleagues used epigenomic data to investigate the mechanistic basis of the strongest genetic association with obesity.[16] They showed that this mechanism operates in the fat cells of both humans and mice and detailed how changes within the relevant genomic regions cause a shift from dissipating energy as heat (thermogenesis) to storing energy as fat.[18] A full understanding of the phenomenon may lead to treatments for people whose 'slow metabolism' cause them to gain excessive weight.[17]

Alzheimer's disease

Kellis, Li-Huei Tsai, and others at MIT used epigenomic markings in human and mouse brains to study the mechanisms leading to Alzheimer’s disease.[20] They showed that immune cell activation and inflammation, which have long been associated with the condition, are not simply the result of neurodegeneration, as some researchers have argued. Rather, in mice engineered to develop Alzheimer’s-like symptoms, they found that immune cells start to change even before neural changes are observed[21]

Genotype-Tissue Expression (GTEx)

Kellis is a member of the Genotype-Tissue Expression (GTEx) project that seeks to elucidate the basis of disease predisposition. It is an NIH-sponsored project that seeks to characterize genetic variation in human tissues with roles in diabetes, heart disease, and cancer.[15]

To date, his lab has developed specific domain expertise in obesity,[17] diabetes,[19] Alzheimer's disease,[20] schizophrenia,[23] and cancer.[24]

Teaching

In addition to his research, Kellis co-taught for several years MIT's required undergraduate introductory algorithm courses 6.006: Introduction to Algorithms and 6.046: Design and Analysis of Algorithms[38][39] with Profs. Ron Rivest, Erik Demaine, Piotr Indyk, Srinivas Devadas and others.

He is also teaching a computational biology course at MIT, titled "Computational Biology: Genomes, Networks, Evolution."[40] The course (6.047/6.878) is geared towards advanced undergraduate and early graduate students, seeking to learn the algorithmic and machine learning foundations of computational biology, and also be exposed to current frontiers of research in order to become active practitioners of the field.[41] He started 6.881: Computational Personal Genomics: Making sense of complete genomes.[42] This course is aimed at exploring the computational challenges associated with interpreting how sequence differences between individuals lead to phenotypic differences such as gene expression, disease predisposition, or response to treatment.[43]

Awards and honors

Kellis received the US Presidential Early Career Award for Scientists and Engineers (PECASE),[44] the National Science Foundation CAREER award,[45] a Sloan Research Fellowship,[46] the Athens Information Technology (AIT) Niki Award for Science and Engineering,[47] the Ruth and Joel Spira Teaching award,[48] and the George M. Sprowls Award for the best Ph.D. thesis in Computer Science at MIT.[27] He was named as one of Technology Review's Top 35 Innovators Under 35 for his research in comparative genomics[49]

Media appearances

  • Decoding A Genomic Revolution, TEDx Cambridge, 2013 "MIT Computational Biologist Manolis Kellis gives us a glimpse of the doctor’s office visit of the future, and uses his own genetic mutations to show itus how a revolution in genomics is unlocking treatments that could transform medicine as we know it"[50]
  • Regulatory Genomics and Epigenomics of Complex Disease, Welcome Trust, 2014 "Manolis Kellis, Massachusetts Institute of Technology, USA, gives one of the keynote lectures at Epigenomics of Common Diseases, (28-31 October 2014), organised by the Wellcome Genome Campus Advanced Courses and Scientific Conferences team at Churchill College, Cambridge[51]
  • Manolis Kellis Reddit Ask Me Anything (AMA), Reddit Science AMA Series: "I’m Manolis Kellis, a professor of computer science at MIT studying the human genome to learn about what causes obesity, Alzheimer’s, cancer and other conditions. AMA about comp-bio and epigenomics, and how they impact human health".

Controversy

In 2014 Nicolas Bray and Lior Pachter from the University of California, Berkeley wrote a series of blog posts about Kellis' work in which they described one of his papers of being dishonest and fraudulent[52]. Specific criticisms included that the method used to obtain the results in Kellis' paper was completely different than the idealized version sold in the main text of the paper, and the method actually used has parameters that need to be set, yet no approach to setting them was provided. Furthermore, Kellis was accused of having deliberately tried to hide the existence of the parameters. Bray and Pachter suggested that the reason for covering up the existence of parameters was that the parameters were tuned to obtain the results. Moreover, they claimed that the results in the paper were not reproducible and that the provided data and software were not enough to replicate even a single figure in the paper. In the blog post Lior Pachter offered $100 to anyone who could replicate the results in the paper, including, crucially, two different versions of a supplementary figure (one of which had been updated by the authors subsequent to publication). As of August 2018 it appears that no one has claimed the award.

References

  1. 1 2 Manolis Kellis publications indexed by Google Scholar Edit this at Wikidata
  2. ↑ Kamvysselis, Manolis (2003). Computational comparative genomics : genes, regulation, evolution. mit.edu (PhD thesis). MIT. hdl:1721.1/7999. OCLC 53277177.
  3. ↑ "Manolis Kellis | MIT CSAIL". www.csail.mit.edu. Retrieved 2018-07-19.
  4. ↑ "MIT Computational Biology Group". MIT Computational Biology Group Lab Head. Retrieved 2018-07-19.
  5. ↑ Kellis, Manolis. "People | MIT CSAIL". www.csail.mit.edu. Retrieved 2018-07-19.
  6. ↑ "Roadmap Epigenomics Project - Home". www.roadmapepigenomics.org. Retrieved 2018-07-24.
  7. 1 2 Kundaje, Anshul; Meuleman, Wouter; Ernst, Jason; Bilenky, Misha; Yen, Angela; Heravi-Moussavi, Alireza; Kheradpour, Pouya; Zhang, Zhizhuo; Kellis, Manolis (2015). "Integrative analysis of 111 reference human epigenomes". Nature. 518 (7539): 317–330. doi:10.1038/nature14248. ISSN 0028-0836.
  8. ↑ "Researchers generate a reference map of the human epigenome". MIT News. Retrieved 2018-07-18.
  9. ↑ "Researchers generate a reference map of the human epigenome". MIT News. Retrieved 2018-07-19.
  10. 1 2 Lindblad-Toh, Kerstin; Garber, Manuel; Zuk, Or; Lin, Michael F.; Parker, Brian J.; Washietl, Stefan; Kheradpour, Pouya; Ernst, Jason; Kellis, Manolis (2011). "A high-resolution map of human evolutionary constraint using 29 mammals". Nature. 478 (7370): 476–482. doi:10.1038/nature10530. ISSN 0028-0836. PMC 3207357.
  11. ↑ "Analysis of 29 mammals reveals genomic 'dark matter'". MIT News. Retrieved 2018-07-21.
  12. ↑ Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E. (2014-04-29). "Defining functional DNA elements in the human genome". Proceedings of the National Academy of Sciences. 111 (17): 6131–6138. doi:10.1073/pnas.1318948111. ISSN 0027-8424. PMID 24753594.
  13. ↑ Ernst, Jason; Kheradpour, Pouya; Mikkelsen, Tarjei S.; Shoresh, Noam; Ward, Lucas D.; Epstein, Charles B.; Zhang, Xiaolan; Wang, Li; Issner, Robbyn (2011-03-23). "Mapping and analysis of chromatin state dynamics in nine human cell types". Nature. 473 (7345): 43–49. doi:10.1038/nature09906. ISSN 0028-0836.
  14. ↑ Consortium, The modENCODE; Roy, Sushmita; Ernst, Jason; Kharchenko, Peter V.; Kheradpour, Pouya; Negre, Nicolas; Eaton, Matthew L.; Landolin, Jane M.; Bristow, Christopher A. (2010-12-24). "Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE". Science. 330 (6012): 1787–1797. doi:10.1126/science.1198374. ISSN 0036-8075. PMID 21177974.
  15. 1 2 3 "Kellis to lead MIT team in new phase of GTEx project to elucidate basis of disease predisposition". MIT News. Retrieved 2018-07-19.
  16. 1 2 "Identifying the gene switch that turns fat cells bad". Science | AAAS. 2015-08-19. Retrieved 2018-07-19.
  17. 1 2 3 "A Fat-Burning Gene May Help Weight Loss". Time. Retrieved 2018-07-19.
  18. 1 2 Claussnitzer, Melina; Dankel, Simon N.; Kim, Kyoung-Han; Quon, Gerald; Meuleman, Wouter; Haugen, Christine; Glunk, Viktoria; Sousa, Isabel S.; Kellis, Manolis (2015-09-03). "FTO Obesity Variant Circuitry and Adipocyte Browning in Humans". New England Journal of Medicine. 373 (10): 895–907. doi:10.1056/nejmoa1502214. ISSN 0028-4793. PMC 4959911. PMID 26287746.
  19. 1 2 Onengut-Gumuscu, Suna; Chen, Wei-Min; Burren, Oliver; Cooper, Nick J; Quinlan, Aaron R; Mychaleckyj, Josyf C; Farber, Emily; Bonnie, Jessica K; Kellis, Manolis (2015-03-09). "Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers". Nature Genetics. 47 (4): 381–386. doi:10.1038/ng.3245. ISSN 1061-4036.
  20. 1 2 3 Gjoneska, Elizabeta; Pfenning, Andreas R.; Mathys, Hansruedi; Quon, Gerald; Kundaje, Anshul; Tsai, Li-Huei; Kellis, Manolis (2015). "Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer's disease". Nature. 518 (7539): 365–369. doi:10.1038/nature14252. ISSN 0028-0836.
  21. 1 2 "Epigenomics of Alzheimer's disease progression". MIT News. Retrieved 2018-07-19.
  22. ↑ "Manolis Kellis – Cure Alzheimer's Fund". Cure Alzheimer's Fund. Retrieved 2018-07-19.
  23. 1 2 Manolis, Kellis; Mark, Daly; Kevin, Eggan; Alkes, Price. "NIH Grant, Network-based prediction and validation of causal schizophrenia genes and variants". Grantome.
  24. 1 2 Hornshøj, Henrik; Nielsen, Morten Muhlig; Sinnott-Armstrong, Nicholas A.; Świtnicki, Michał P.; Juul, Malene; Madsen, Tobias; Sallari, Richard; Kellis, Manolis; Ørntoft, Torben (2018-01-11). "Pan-cancer screen for mutations in non-coding elements with conservation and cancer specificity reveals correlations with expression and survival". Npj Genomic Medicine. 3 (1): 1. doi:10.1038/s41525-017-0040-5. ISSN 2056-7944. PMC 5765157. PMID 29354286.
  25. ↑ "Getting to the root of genetics". MIT News. Retrieved 2018-07-19.
  26. 1 2 "Manolis Kellis MIT Center for Genome Research Resume" (PDF).
  27. 1 2 "All Awards | MIT CSAIL". csail.mit.edu. Retrieved 2018-07-19.
  28. ↑ "Kanellakis Fellowships | MIT EECS". www.eecs.mit.edu. Retrieved 2018-07-19.
  29. ↑ pubmeddev. "Manolis Kellis - PubMed - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-07-19.
  30. ↑ "NIH-supported researchers map epigenome of more than 100 tissue and cell types". National Institutes of Health (NIH). 2015-07-03. Retrieved 2018-07-19.
  31. ↑ Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E. (2014-04-29). "Defining functional DNA elements in the human genome". Proceedings of the National Academy of Sciences of the United States of America. 111 (17): 6131–6138. doi:10.1073/pnas.1318948111. ISSN 0027-8424. PMC 4035993. PMID 24753594.
  32. ↑ Kellis, Manolis; Patterson, Nick; Endrizzi, Matthew; Birren, Bruce; Lander, Eric S. (2003). "Sequencing and comparison of yeast species to identify genes and regulatory elements". Nature. 423 (6937): 241–254. doi:10.1038/nature01644. ISSN 0028-0836.
  33. 1 2 3 4 Schaffer, Amanda. "Annotating the book of life". MIT Technology Review. Retrieved 2018-07-19.
  34. ↑ Xie, Xiaohui; Lu, Jun; Kulbokas, E. J.; Golub, Todd R.; Mootha, Vamsi; Lindblad-Toh, Kerstin; Lander, Eric S.; Kellis, Manolis (2005-02-27). "Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals". Nature. 434 (7031): 338–345. doi:10.1038/nature03441. ISSN 0028-0836.
  35. ↑ Lin, Michael F.; Carlson, Joseph W.; Crosby, Madeline A.; Matthews, Beverley B.; Yu, Charles; Park, Soo; Wan, Kenneth H.; Schroeder, Andrew J.; Kellis, Manolis (2007). "Revisiting the protein-coding gene catalog of Drosophila melanogaster using 12 fly genomes". Genome Research. 17 (12): 1823–1836. doi:10.1101/gr.6679507. ISSN 1088-9051. PMC 2099591. PMID 17989253.
  36. ↑ Stark, Alexander; Lin, Michael F.; Kheradpour, Pouya; Pedersen, Jakob S.; Parts, Leopold; Carlson, Joseph W.; Crosby, Madeline A.; Rasmussen, Matthew D.; Kellis, Manolis (2007). "Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures". Nature. 450 (7167): 219–232. doi:10.1038/nature06340. ISSN 0028-0836.
  37. ↑ Kellis, Manolis; Birren, Bruce W.; Lander, Eric S. (2004-03-07). "Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae". Nature. 428 (6983): 617–624. doi:10.1038/nature02424. ISSN 0028-0836.
  38. ↑ "6.006: Introduction to Algorithms - Massachusetts Institute of Technology". courses.csail.mit.edu. Retrieved 2018-07-19.
  39. ↑ "6.046/18.410 Class Home". stellar.mit.edu. Retrieved 2018-07-20.
  40. ↑ "6.047/6.878 Class Home". stellar.mit.edu. Retrieved 2018-07-19.
  41. ↑ "Computational Biology". MIT OpenCourseWare. Retrieved 2018-07-19.
  42. ↑ "6.881 Computational Personal Genomics: Making sense of complete genomes | MIT EECS". www.eecs.mit.edu. Retrieved 2018-07-19.
  43. ↑ "Computational Personal Genomics: Making Sense of Complete Genomes". MIT OpenCourseWare. Retrieved 2018-07-19.
  44. ↑ "Aaronson, Kellis recipients of PECASE 2010 Award | MIT EECS". www.eecs.mit.edu. Retrieved 2018-07-19.
  45. ↑ "NSF Award Search: Award#0644282 - CAREER: Comparative Genomics and Biological Signal Discovery in the Human Genome". www.nsf.gov. Retrieved 2018-07-19.
  46. ↑ "Sloan Foundation Fellows". sloan.org. Retrieved 2018-07-19.
  47. ↑ "Kellis Wins Niki Award | MIT CSAIL". www.csail.mit.edu. Retrieved 2018-07-19.
  48. ↑ "MIT School of Engineering | » Teaching Awards". Mit Engineering. Retrieved 2018-07-19.
  49. ↑ MIT Technology Review. "Innovator Under 35: Manolis Kellis, 29". MIT Technology Review. Retrieved 2018-07-19.
  50. ↑ "Decoding A Genomic Revolution | TEDxCambridge". TEDxCambridge. Retrieved 2018-07-19.
  51. ↑ Wellcome Genome Campus Courses and Conferences (2016-02-25), Regulatory Genomics and Epigenomics of Complex Disease - Manolis Kellis, retrieved 2018-07-19
  52. ↑ "The network nonsense of Manolis Kellis". liorpachter.wordpress.com. Retrieved 2018-08-25.


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