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Computational and Statistical Genomics Lab

The CSG Lab combines novel computational approaches with large-scale genomics data to characterize the regulatory programs that underlie gene expression.

RESEARCH IN THE CSG LAB

The genome serves as a blueprint of the body, with highly detailed regulatory instructions that activate, repress, or modify dynamic programs of gene expression across cell types and tissues. The gene products, in turn, are responsible for reading and executing these regulatory instructions. At the CSG lab, we develop computational methods to characterize these regulatory instructions, understand how proteins and other gene products interpret them, and create models that predict how defects in these instructions can affect the cell function and, eventually, human health.


Our research encompasses the study of transcription factors, RNA-binding proteins, and non-coding RNAs. We combine machine learning and statistical inference with large genomics datasets to characterize gene regulatory networks of these factors, genetic determinants of variation in their regulatory programs, and their association with human diseases.

TRANSCRIPTIONAL REGLUATION

The human genome encodes more than 1700 transcription factors, representing a massively complex system in which hundreds of proteins work together to affect chromatin organization and gene expression. We combine machine-learning with genomics and transcriptomics data to develop predictive models of DNA-binding by transcription factors, understand how they interact with different components of the chromatin, and reveal their role in regulating the chromatin state and gene expression.

Selected publications:

Najafabadi et al., Nat Biotechnol 2015, 33:555
Schmitges et al., Genome Res 2016, 26:1742
Najafabadi et al., Genome Biol 2017, 18:167

REGULATION OF RNA STABILITY

The abundance of each mRNA is determined by the balance between its production and decay rates. A large number of factors in the human cell can potentially influence mRNA stability, including more than 390 RNA-binding proteins and 3,600 microRNAs. We develop novel algorithms that enable us to measure mRNA stability from transcriptome profiling data, and use them to uncover the roles of RNA-binding proteins and microRNAs in regulating the stability of various mRNAs across different tissues and cell types.

Selected publications:

Alkallas et al., Nat Commun 2017, 8:909
Goodarzi et al., Nature 2012, 485:264
Ray et al., Nature 2013, 499:172

DYSREGULATED PROGRAMS IN CANCER

Various human diseases, from metabolic disorders to developmental disorders and cancer, can be caused by defects in regulatory programs that modulate gene expression at transcriptional or post-transcriptional level. A main focus of our research is to identify factors whose dysregulation drives the development and progression of cancer, by combining novel computational methods with large compendiums of genomics, epigenomics and transcriptomics data from cancer patients.

Selected publications:

Goodarzi et al., Nature 2012, 485:264
Jandaghi et al., Gastroenterology 2016, 151:1218

PUBLICATIONS

* Corresponding author
† Equal contribution


– – – – – – 2017 – – – – – –


Alkallas R, Fish L, Goodarzi H, Najafabadi HS * (2017). Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer's disease. Nat Commun 8:909. PMID 29030541

Supplementary data: Visit the web supplement.
Software: Download the source code.



Najafabadi HS *, Garton M, Weirauch MT, Mnaimneh S, Yang A, Kim PM, Hughes TR * (2017). Non-base-contacting residues enable kaleidoscopic evolution of metazoan C2H2 zinc finger DNA binding. Genome Biol 18:167. PMID 28877740

Related links: See Research Highlight by Alba MM.


– – – – – – 2016 – – – – – –


Schmitges FW †, Radovani E †, Najafabadi HS †, Barazandeh M †, Campitelli LF †, Yin Y, Jolma A, Zhong G, Guo H, Kanagalingam T, Dai WF, Taipale J, Emili A, Greenblatt JF, Hughes TR (2016). Multiparameter functional diversity of human C2H2 zinc finger proteins. Genome Res 26:1742-1752. PMID 27852650

Supplementary data: Visit the web supplement.


Jandaghi P, Najafabadi HS, Bauer AS, Papadakis AI, Fassan M, Hall A, Monast A, von Knebel Doeberitz M, Neoptolemos JP, Costello E, Greenhalf W, Scarpa A, Sipos B, Auld D, Lathrop M, Park M, Büchler MW, Strobel O, Hackert T, Giese NA, Zogopoulos G, Sangwan V, Huang S, Riazalhosseini Y, Hoheisel JD (2016). Expression of DRD2 is Increased in Human Pancreatic Ductal Adenocarcinoma and Inhibitors Slow Tumor Growth in Mice. Gastroenterology 151:1218-1231. PMID 27578530


Lambert SA, Albu M, Hughes TR *, Najafabadi HS * (2016). Motif comparison based on similarity of binding affinity profiles. Bioinformatics 32:3504-3506. PMID 27466627

Software: Download the source code, or use the online web server.


Gazestani VH, Nikpour N, Mehta V, Najafabadi HS, Moshiri H, Jardim A, Salavati R (2016). A Protein Complex Map of Trypanosoma brucei. PLoS Negl Trop Dis 10:e0004533. PMID: 26991453


– – – – – – 2015 – – – – – –


Garton M, Najafabadi HS, Schmitges FW, Radovani E, Hughes TR, Kim PM (2015). A structural approach reveals how neighbouring C2H2 zinc fingers influence DNA binding specificity. Nucleic Acids Res 43:9147-9157. PMID: 26384429


Najafabadi HS, Albu M, Hughes TR (2015). Identification of C2H2-ZF binding preferences from ChIP-seq data using RCADE. Bioinformatics 31:2879-81. PMID: 25953800

Software: Download the source code, or use the online web server.


Narasimhan K, Lambert SA, Yang AW, Riddell J, Mnaimneh S, Zheng H, Albu M, Najafabadi HS, Reece-Hoyes JS, Fuxman Bass JI, Walhout AJ, Weirauch MT, Hughes TR (2015). Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities. eLife doi:10.7554/eLife.06967. PMID: 25905672


Najafabadi HS †, Mnaimneh S †, Schmitges FW †, Garton M, Lam K, Yang A, Albu M, Weirauch MT, Radovani E, Kim PM, Greenblatt J, Frey BJ, Hughes TR (2015). C2H2 zinc finger proteins greatly expand the human regulatory lexicon. Nat Biotechnol 33:555-562. PMID: 25690854

Supplementary data: Visit the web supplement.


Xiong HY, Alipanahi B, Lee LJ, Bretschneider H, Merico D, Yuen RK, Hua Y, Gueroussov S, Najafabadi HS, Hughes TR, Morris Q, Barash Y, Krainer AR, Jojic N, Scherer SW, Blencowe BJ, Frey BJ (2015). The human splicing code reveals new insights into the genetic determinants of disease. Science 347:1254806. PMID: 25525159


Razavi R, Najafabadi HS, Abdullah S, Smukler S, Arntfield M, van der Kooy D (2015). Diabetes enhances the proliferation of adult pancreatic multipotent progenitor cells and biases their differentiation to more β-cell production. Diabetes 64:1311-23. PMID: 25392245


– – – – – – 2014 – – – – – –


Weirauch MT, Yang A, Albu M, Cote A, Montenegro-Montero A, Drewe P, Najafabadi HS, Lambert SA, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano JC, Galli M, Lewsey M, Huang E, Mukherjee T, Chen X, Reece-Hoyes JS, Govindarajan S, Shaulsky G, Walhout AJ, Bouget F, Ratsch G, Larrondo LF, Ecker JR, and Hughes TR (2014). Determination and inference of Eukaryotic transcription factor sequence specificity. Cell 158:1431-1443. PMID: 25215497


– – – – – – 2013 – – – – – –


Najafabadi HS †, Lu Z †, MacPherson C, Mehta V, Adoue V, Pastinen T, Salavati R (2013). Global identification of conserved post-transcriptional regulatory programs in trypanosomatids. Nucleic Acids Res 41:8591-8600. PMID: 23877242


Ray D †, Kazan H †, Cook K †, Weirauch M †, Najafabadi HS †, Li X, Albu M, Zheng H, Yang A, Na H, Guerrousov S, Irimia M, Matzat L, Dale R, Smith S, Yarosh C, Kelly S, Nabet B, Mecenas D, Li W, Laishram R, Qiao M, Lipshitz H, Piano F, Corbett A, Carstens R, Frey B, Anderson R, Lynch K, Penalva L, Lei E, Blencowe B, Fraser A, Morris Q, Hughes T (2013). A compendium of RNA binding motifs for decoding gene regulation. Nature 499:172–177. PMID: 23846655


– – – – – – 2012 – – – – – –


Goodarzi H, Najafabadi HS, Oikonomou P, Greco TM, Fish L, Salavati R, Cristea IM, Tavazoie S (2012). Systematic discovery of structural elements governing stability of mammalian messenger RNAs. Nature 485:264-8. PMID: 22495308


– – – – – – 2011 – – – – – –


Moshiri H, Acoca S, Kala S, Najafabadi HS, Hogues H, Purisima E, Salavati R (2011). Naphthalene-based RNA editing inhibitor blocks RNA editing activities and editosome assembly in Trypanosoma brucei. J Biol Chem 286:14178-89. PMID: 21378165


– – – – – – 2010 – – – – – –


Najafabadi HS, Salavati R (2010). Functional genome annotation by combined analysis across microarray studies of Trypanosoma brucei. PLoS Negl Trop Dis 4:e810. PMID: 20824174


Salavati R, Najafabadi HS (2010). Sequence-based functional annotation: what if most of the genes are unique to a genome? Trends Parasitol 26:225-229. PMID: 20211583


– – – – – – 2009 – – – – – –


Najafabadi HS †, Goodarzi H †, Salavati R (2009). Universal function-specificity of codon usage. Nucleic Acids Res 37:7014-23. PMID: 19773421


Mao Y †, Najafabadi HS †, Salavati R (2009). Genome-wide computational identification of functional RNA elements in Trypanosoma brucei. BMC Genomics 10:355. PMID: 19653906


Azizi H, Hassani K, Taslimi Y, Najafabadi HS, Papadopoulou B, Rafati S (2009). Searching for virulence factors in the non-pathogenic parasite to humans Leishmania tarentolae. Parasitology 136:723-35. PMID: 19416551


– – – – – – 2008 – – – – – –


Najafabadi HS, Salavati R (2008). Sequence-based prediction of protein-protein interactions by means of codon usage. Genome Biol 9:R87. PMID: 18501006


Najafabadi HS, Torabi N, Chamankhah M (2008). Designing multiple degenerate primers via consecutive pairwise alignments. BMC Bioinformatics 9:55. PMID: 18221562


Najafabadi HS, Saberi A, Torabi N, Chamankhah M (2008). MAD-DPD: designing highly degenerate primers with maximum amplification specificity. Biotechniques 44:519-526. PMID: 18476816


– – – – – – 2007 – – – – – –


Goodarzi H, Torabi N, Najafabadi HS, Archetti M (2007). Amino Acid and Codon Usage Profiles: Adaptive Changes in the Frequency of Amino Acids and Codons. Gene 407:30-41. PMID: 17977670


Goodarzi H, Katanforoush A, Torabi N, Najafabadi HS (2007). Solvent accessibility, residue charge and residue volume, the three ingredients of a robust amino acid substitution matrix. J Theor Biol 245:715-725. PMID: 17240399


– – – – – – 2006 – – – – – –


Najafabadi HS *, Lehmann J, Omidi M (2006). Error minimization explains the codon usage of highly expressed genes in Escherichia coli. Gene 387:150-155. PMID: 17097242


Torabi N, Goodarzi H, Najafabadi HS (2006). The case for an error minimizing set of coding amino acids. J Theor Biol 244:737-744. PMID: 17069856


Najafabadi HS *, Goodarzi H, Torabi N (2006). Applying a neural network to predict the thermodynamic parameters for an expanded nearest neighbor model. J Theor Biol 238:657-665. PMID: 16061260


– – – – – – 2005 – – – – – –


Goodarzi H, Najafabadi HS, Torabi N (2005). On the coevolution of genes and genetic code. Gene 362:133-140. PMID: 16213111


Najafabadi HS *, Goodarzi H, Torabi N (2005). Optimality of codon usage in Escherichia coli due to load minimization. J Theor Biol 237:203-209. PMID: 15932760


Goodarzi H, Najafabadi HS, Torabi N (2005). The impact of including tRNA content on the optimality of the genetic code. Bull Math Biol 67:1355-1368. PMID: 16005951


Goodarzi H, Najafabadi HS, Torabi N (2005). On the optimality of the genetic code, with the consideration of coevolution theory by comparison of prominent cost measure matrices. J Theor Biol 235:318-325. PMID: 15882694


Goodarzi H, Najafabadi HS, Torabi N (2005). Designing a neural network for the constraint optimization of the fitness functions devised based on the load minimization of the genetic code. Biosystems 81:91-100. PMID: 15936137

LAB MEMBERS

Hamed S. Najafabadi
Principal Investigator

Berat Dogan
Postdoctoral Fellow

Gabrielle Perron
Graduate Student
(with Yasser Riazalhosseini)

Rached Alkallas
Graduate Student
(with Ian R. Watson)

Larry Dong
Undergraduate Research Assistant

 

FORMER LAB MEMBERS

Aldo Hernández Corchado
Mitacs Globalink Research Intern
Current position: Undergraduate student, Monterrey Institute of Technology and Higher Education, Mexico

 

Colleen Rollins
Undergraduate Research Assistant
Current position: Graduate student, University of Cambridge, UK

LAB NEWS

October 13, 2017

Our paper on the inference of mRNA stability from RNA-seq data is now published in Nature Communications!

In this paper, we introduce a new method for inferring differential mRNA stability based on intronic and exonic reads in RNA-seq data, and use it to investigate the post-transcriptional regulatory programs of human brain and Alzheimer's disease.

May 18, 2017

Congratulations to Rached Alkallas on receiving the best poster award at the Human Genetics Research Day!

Rached's presentation on our new method for estimating mRNA stability from RNA-seq data was selected for the best M.Sc. poster award at the Human Genetics Research Day.

May 15, 2017

Congratulations to Gabrielle Perron on receiving the FRQS training award!

Gabrielle has been awarded a two-year M.Sc. FRQS training scholarship for her work on "modeling the role of RNA-binding proteins in regulation of the stability of messenger RNAs".

April 4, 2017

Congratulations to Colleen Rollins on receiving the Gates Cambridge Scholarship!

Colleen has received the prestigous Gates Cambridge Scholarship, and will join the University of Cambridge in September to pursue a Ph.D. degree in psychiatry.

November 14, 2016

Congratulations to Dr. Berat Dogan on receiving the TUBITAK Postdoctoral Fellowship!

Berat has received the prestiguous TUBITAK Postdoctoral Fellowship from the Scientific and Technological Research Council of Turkey, and will join us in in 2017 to work on predictive models of DNA binding by Cys2His2 zinc finger proteins.

May 22, 2016

Congratulations to Pubudu Nawarathna on receiving the Queen Elizabeth II Diamond Jubilee Scholarship!

Pubudu will join us in September as a graduate student of Human Genetics.

AVAILABLE POSITIONS

GRADUATE STUDENT

We are looking for motivated graduate students at the M.Sc. or Ph.D. level. Interested applicants should send their CV, a statement of research interests, a copy of their academic transcripts, and the contact information of at least two references to hamed.najafabadi@mcgill.ca.

POSTDOCTORAL FELLOW

We are recruiting postdoctoral fellows with expertise in developing and applying innovative computational methods for solving problems related to functional genomics and epigenomics. Interested applicants should send a cover letter, CV, and the contact information of at least three references to hamed.najafabadi@mcgill.ca.

ADDRESS

McGill University and Génome Québec Innovation Centre
740 Dr. Penfield Avenue, Room 7202
Montréal, Québec, H3A 0G1, Canada


CONTACT


Hamed S. Najafabadi, Ph.D.

Assistant Professor, Department of Human Genetics, McGill University

Office: (514) 398-5308

Email: hamed.najafabadi@mcgill.ca

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