Computational and Statistical Genomics Lab

RESEARCH AT THE CSG LAB

The genome provides a detailed blueprint for the body, with complex regulatory instructions that determine each cell's state and function. Cell state, in turn, determines how these instructions are interpreted and executed. At the CSG Lab, we develop data-driven computational methods to decode these regulatory instructions, aiming to understand how their malfunction can disrupt cellular behaviour and ultimately impact human health.

Our research focuses on uncovering the regulatory programs governed by transcription factors, RNA-binding proteins, and non-coding RNAs. By combining machine learning and statistical approaches with large-scale genomics data, we create models that reveal the roles of these factors in defining cell identity and function, providing insights into the molecular basis of human diseases.

MEASURING GENE REGULATION ACROSS LAYERS

The abundance of each mRNA is shaped by the combined effects of its production, processing, and decay rates. Understanding these processes begins with accurate quantification. We combine omics technologies with novel statistical algorithms to quantify mRNA regulation—from transcription through decay and from single cells to large patient cohorts.

Example publications:

Apostolides et al., bioRxiv, 2024
Madrigal et al., Nat Commun, 2024
Farouni et al., Nat Commun, 2020
Alkallas et al., Nat Commun, 2017

SEQUENCE-TO-ACTIVITY MODELS OF GENE REGULATION

The multiple layers of mRNA regulation are governed by an extraordinarily complex network involving millions of cis-regulatory elements and trans-acting factors. We use machine learning to develop models that decode these regulatory instructions and map their interactions with transcription factors, RNA-binding proteins, and microRNAs, ultimately shaping the cell's mRNA landscape.

Example publications:

Saberi et al., bioRxiv, 2024
Corchado and Najafabadi, Genome Biol, 2022
Najafabadi et al., Nat Biotechnol, 2015
Goodarzi et al., Nature, 2012

GENE REGULATORY BASIS OF CANCER

Disruptions in gene regulation drive the extensive transformation of cancer cell identity and behavior. We apply omics technologies to measure these disruptions across all layers of mRNA regulation and develop algorithms to identify the dysregulated factors that fuel cancer development and progression. 


Example publications:

Perron et al., Commun Biol, 2022
Fish et al., Science, 2021
Perron et al., Cell Rep, 2018

PUBLICATIONS

* Corresponding author
† Equal contribution

– – – – – – Preprints – – – – – –


Saberi A †, Choi B †, Wang S, Corchado AH, Naghipourfar M, Dandage R, Namini AM, Ramani V *, Emad A *, Najafabadi HS *, Hani Goodarzi * (2024). A long-context RNA foundation model for predicting transcriptome architecture. bioRxiv DOI:10.1101/2024.08.26.609813.

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


Apostolides M †, Choi B †, Navickas A, Saberi A, Soto LM, Goodarzi H *, Najafabadi HS * (2024). Accurate isoform quantification by joint short-and long-read RNA-sequencing. bioRxiv DOI:10.1101/2024.07.11.603067.

Software: Download the source code.


Jolma A †, Corchado AH †, Yang AWH †, Fathi A †, Laverty KU †, Brechalov A, Razavi R, Albu M, Zheng H, The Codebook Consortium, Kulakovskiy IV, Najafabadi HS *, Hughes TR * (2024). GHT-SELEX demonstrates unexpectedly high intrinsic sequence specificity and complex DNA binding of many human transcription factors. bioRxiv DOI:10.1101/2024.11.11.618478.

Supplementary data and code: Visit the web supplement.
Software: Download the source code for MAGIX and RCADEEM.


Razavi R, Fathi A, Yellan I, Brechalov A, Laverty KU, Jolma A, Corchado AH, Zheng H, Yang AWH, Albu M, Barazandeh M, Hu C, Vorontsov IE, Patel ZM, The Codebook Consortium, Kulakovskiy IV, Bucher P, Morris Q, Najafabadi HS, Hughes TR (2024). Extensive binding of uncharacterized human transcription factors to genomic dark matter. bioRxiv DOI:10.1101/2024.11.11.622123


Jolma A, Laverty KU, Fathi A, Yang AWH, Yellan I, Vorontsov IE, Inukai S, Kribelbauer-Swietek JF, Gralak AJ, Razavi R, Albu M, Brechalov A, Patel ZM, Nozdrin V, Meshcheryakov G, Kozin I, Abramov S, Boytsov A, The Codebook Consortium, Fornes O, Makeev VJ, Grau J, Grosse I, Bucher P, Deplancke B, Kulakovskiy IV, Hughes TR (2024). Perspectives on Codebook: sequence specificity of uncharacterized human transcription factors. bioRxiv DOI:10.1101/2024.11.11.622097


Vorontsov IE, Kozin I, Abramov S, Boytsov A, Jolma A, Albu M, Ambrosini G, Faltejskova K, Gralak AJ, Gryzunov N, Inukai S, Kolmykov S, Kravchenko P, Kribelbauer-Swietek JF, Laverty KU, Nozdrin V, Patel ZM, Penzar D, Plescher ML, Pour SE, Razavi R, Yang AWH, Yevshin I, Zinkevich A, Weirauch MT, Bucher P, Deplancke B, Fornes O, Grau J, Grosse I, Kolpakov FA, The Codebook/GRECO-BIT Consortium, Makeev VJ, Hughes TR, Kulakovskiy IV (2024). Cross-platform DNA motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors. bioRxiv DOI:10.1101/2024.11.11.619379


Gralak AJ, Faltejskova K, Yang AWH, Steiner C, Russeil J, Grenningloh N, Inukai S, Demir M, Dainese R, Owen C, Pankevich E, The Codebook/GRECO-BIT Consortium, Hughes TR, Kulakovskiy IV, Kribelbauer-Swietek JF, van Mierlo G, Deplancke B (2024). Identification of methylation-sensitive human transcription factors using meSMiLE-seq. bioRxiv DOI:10.1101/2024.11.11.619598

– – – – – – 2024 – – – – – –


Madrigal A, Lu T, Soto LM, Najafabadi HS *. A unified model for interpretable latent embedding of multi-sample, multi-condition single-cell data. Nat Commun 15:6573. PMID 39097589.

Software: Download the source code.
Code: Download the reproducible analysis notebooks.


Zhang W *, Sladek R, Li Y, Najafabadi HS, Josee Dupuis * (2024). Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro. Nat Commun 15:9374. PMID 39478020.


Blackburn DM, Sahinyan K, Corchado AH, Lazure F, Richard V, Raco L, Perron G, Zahedi RP, Borchers CH, Lepper C, Kawabe H, Jahani-Asl A, Najafabadi HS, Soleimani V (2024). The E3 Ubiquitin Ligase Nedd4L Preserves Skeletal Muscle Stem Cell Quiescence by Inhibiting their Activation. iScience 27:110241. PMID 39015146 .


Burban A, Sharanek A, Corchado AH, Najafabadi HS, Soleimani V, Jahani-Asl A (2024). Targeting glioblastoma with a brain-penetrant drug that impairs brain tumor stem cells via NLE1-Notch1 complex. Stem Cell Reports 19:1534. PMID 39423824.


Zhang W *, Lu T, Sladek R, Li Y, Najafabadi HS, Josee Dupuis * (2024). SharePro: an accurate and efficient genetic colocalization method accounting for multiple causal signals. Bioinformatics 40:btae295. PMID 38688586.


Rasool D, Burban A, Sharanek A, Madrigal A, Hu J, Yan K, Qu D, Voss AK, Slack RS, Thomas T, Bonni A, Picketts DJ, Soleimani VD, Najafabadi HS *, Jahani-Asl A * (2024). PHF6-mediated transcriptional control of NSC via Ephrin receptors is impaired in the intellectual disability syndrome BFLS. EMBO Rep 25:1256. PMID 38429579.


Thivierge C, Bellefeuille M, Diwan S, Dyakov BJA, Leventis R, Perron G, Najafabadi HS, Gravel SP, Gingras AC, Duchaine TF (2024). Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ. Cell Rep 11:2704. PMID 39250314.

– – – – – – 2023 – – – – – –


Lazure F †, Farouni R †, Sahinyan K, Blackburn DM, Corchado AH, Perron G, Lu T, Osakwe A, Ragoussis J, Crist C, Perkins TJ, Jahani-Asl A, Najafabadi HS *, Soleimani VD * (2023). Transcriptional Reprogramming of Skeletal Muscle Stem Cells by the Niche Environment. Nat Commun, 14:535. PMID 36726011

Code: Download the reproducible notebooks.


Zhang W, Najafabadi HS, Li Y (2023). SparsePro: an efficient genome-wide fine-mapping method integrating summary statistics and functional annotations. PLoS Genet, 19(12):e1011104, PMID 38153934

Software: Download the source code.


Ray D, Laverty KU, Jolma A, Nie K, Samson R, Pour SE, Tam CL,  von Krosigk N, Nabeel-Shah S, Albu M, Zheng H, Perron G, Lee H, Najafabadi HS, Blencowe B, Greenblatt J, Morris Q, Hughes TR (2023). RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific. Sci Rep, 13:5238. PMID 37002329.


Kejiou NS, Ilan L, Aigner S, Luo E, Tonn T, Ozadam H, Lee M, Cole GB, Rabano I, Rajakulendran N, Yee BA, Najafabadi HS, Moraes TF, Angers S, Yeo GW, Cenik C, Palazzo AF (2023). Pyruvate Kinase M (PKM) binds ribosomes in a poly-ADP ribosylation dependent manner to induce translational stalling. Nucleic Acids Res, 51(12):6461-6478. PMID 37224531.

– – – – – – 2022 – – – – – –


Perron G, Jandaghi P, Moslemi E, Nishimura T, Rajaee M, Alkallas R, Lu T, Riazalhosseini Y,  Najafabadi HS * (2022). Pan-cancer analysis of mRNA stability for decoding tumour post-transcriptional programs. Commun Biol, 5:851. PMID 35987939.

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


Corchado AH, Najafabadi HS * (2022). Toward a base-resolution panorama of the in vivo impact of cytosine methylation on transcription factor binding. Genome Biol, 23:151. PMID 35799193.

Software: Download the source code.
Supplementary data: Visit the Zenodo repository.


Moldoveanu D, Ramsay L, Lajoie M, Anderson-Trocme L, Lingrand M, Berry D, Perus LJM, Wei Y, Moraes C, Alkallas R, Rajkumar S, Zuo D, Dankner M, Xu EH, Bertos NR, Najafabadi HS, Gravel S, Costantino S, Richer MJ, Lund AW, Del Rincon SV, Spatz A, Miller WH Jr, Jamal R, Lapointe R, Mes-Masson AM, Turcotte S, Petrecca K, Dumitra S, Meguerditchian AN, Richardson K, Tremblay F, Wang B, Chergui M, Guiot MC, Watters K, Stagg J, Quail DF, Mihalcioiu C, Meterissian S, Watson IR (2022). Spatially mapping the immune landscape of melanoma using imaging mass cytometry. Sci Immunol, 7:eabi5072. PMID 35363543.


Alkallas R, Najafabadi HS * (2022). Analysis of mRNA dynamics using RNA sequencing data. In: Jahani-Asl A (eds) Neuronal Cell Death. Methods Mol Biol 2515:129-150. Humana Press, New York, NY. PMID 35776350.

– – – – – – 2021 – – – – – –


Sharanek A, Burban A, Corchado AH, Madrigal A, Fatakdawala I, Najafabadi HS, Soleimani VD, Jahani-Asl A (2021). Transcriptional control of brain tumor stem cells by a carbohydrate binding protein. Cell Rep, 36:109647. PMID 34469737.


Fish L, Khoroshkin M, Navickas A, Garcia K, Culbertson B, Hänisch B, Zhang S, Nguyen H, Soto LM, Dermit M, Mardakheh FK, Molina H, Alarcón C, Najafabadi HS, Goodarzi H (2021). A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements. Science, 372:eabc7531. PMID 33986153.


Tawil N, Bassawon R, Meehan B, Nehme A, Montermini L, Gayden T, De Jay N, Spinelli C, Chennakrishnaiah S, Choi D, Adnani L, Zeinieh M, Jabado N, Kleinman CL, Witcher M, Riazalhosseini Y, Key NS, Schiff D, Grover SP, Mackman N, Couturier CP, Petrecca K, Suvà ML, Patel A, Tirosh I, Najafabadi HS, Rak J (2021). Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles. Blood Adv, 5:1682-1694. PMID 33720339.

– – – – – – 2020 – – – – – –


Farouni R *, Djambazian H, Ferri LE, Ragoussis J,  Najafabadi HS * (2020). Model-based analysis of sample index hopping reveals its widespread artifacts in multiplexed single-cell RNA-sequencing. Nat Commun 11:2704. PMID 32483174.

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


Alkallas R †, Lajoie M †, Moldoveanu D, Hoang K, Lefrançois P, Lingrand M, Ahanfeshar-Adams M, Watters K, Spatz A, Zippin JH, Najafabadi HS, Watson IR (2020). Multi-omic analysis reveals significantly mutated genes and DDX3X as a sex-specific tumor suppressor in cutaneous melanoma. Nat Cancer 1:635-652.


Lazure F, Blackburn DM, Corchado AH, Sahinyan K, Karam N, Sharanek A, Nguyen D, Lepper C, Najafabadi HS, Perkins TJ, Jahani-Asl A, Soleimani VD (2020). Myf6/MRF4 is a myogenic niche regulator required for the maintenance of the muscle stem cell pool. EMBO Rep 21:e49499. PMID 33047485.


Couturier CP, Ayyadhury S, Le PU, Nadaf J, Monlong J, Riva G, Allache R, Baig S, Yan X, Bourgey M, Lee C, Wang YC, Yong VW, Guiot M, Najafabadi HS, Misic B, Antel J, Bourque G, Ragoussis J, Petrecca K (2020). Single-cell RNA-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. Nat Commun 11:3406. PMID 32641768.

– – – – – – 2019 – – – – – –


Blackburn DM, Lazure F, Corchado AH, Perkins TJ, Najafabadi HS, Soleimani VD (2019). High resolution genome wide expression analysis of single myofibers using SMART-Seq. J Biol Chem 294:20097-20108. PMID 31753917.


Fish L, Navickas A, Culbertson B, Xu Y, Nguyen HCB, Zhang S, Hochman M, Okimoto R, Dill BD, Molina H, Najafabadi HS, Alarcón C, Ruggero D, Goodarzi H (2019). Nuclear TARBP2 Drives Oncogenic Dysregulation of RNA Splicing and Decay. Mol Cell 75:967-981. PMID 31300274.


Buckley MA, Woods NT, Tyrer JP, Mendoza-Fandiño G, Lawrenson K, Hazelett DJ, Najafabadi HS, Gjyshi A, Carvalho RS, Lyra PC, Coetzee SG, Shen HC, Yang AW, Earp MA, Yoder S, Risch H, Chenevix-Trench G, Ramus SJ, Phelan CM, Coetzee GA, Noushmehr H, Hughes TR, Sellers TA, Goode EL, Pharoah PDP, Gayther SA, Monteiro AN (2019). Functional analysis and fine mapping of the 9p22.2 ovarian cancer susceptibility locus. Cancer Res 79:467-481. PMID 30487138.


Feulner L, Najafabadi HS, Tanguay S, Rak J, Riazalhosseini Y (2019). Age-related variations in gene expression patterns of renal cell carcinoma. Urol Oncol 37:166-175. PMID 30478010.

– – – – – – 2018 – – – – – –


Dogan B,  Najafabadi HS * (2018). Computational methods for analysis of the DNA-binding preferences of Cys2His2 zinc-finger proteins. In: Liu J (eds) Zinc Finger Proteins. Methods Mol Biol 1867:15-28. Humana Press, New York, NY. PMID 30155812.


Perron G †, Jandaghi P †, Solanki S, Safisamghabadi M, Storoz C, Karimzadeh M, Papadakis AI, Arseneault M, Scelo G, Banks RE, Tost J, Lathrop M, Tanguay S, Brazma A, Huang S, Brimo F, Najafabadi HS *, Riazalhosseini Y * (2018). A general framework for interrogation of mRNA stability programs identifies RNA-binding proteins that govern cancer transcriptomes. Cell Rep 23:1639-1650. PMID 29742422.

Supplementary data: Visit the web supplement.


Karimzadeh M, Jandaghi P, Papadakis AI, Trainor S, Rung J, Gonzàlez-Porta M, Scelo G, Vasudev NS, Brazma A, Huang S, Banks RE, Lathrop M, Najafabadi HS, Riazalhosseini Y (2018). Aberration hubs in protein interaction networks highlight actionable targets in cancer. Oncotarget 9:25166-25180. PMID  29861861.


– – – – – – 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



For older publications, click here.

LAB MEMBERS

Hamed S. Najafabadi

Principal Investigator

Hamed obtained his PhD from McGill University in 2012, followed by a postdoctoral fellowship at the University of Toronto. He returned to McGill University in 2016 as a faculty member and now serves as an Associate Professor of Human Genetics. He also holds a Canada Research Chair in Systems Biology of Gene Regulation and was awarded the Alfred P. Sloan Research Fellowship in Computational & Evolutionary Molecular Biology in 2018. He is a Core Member of the McGill Institute of Genomic Medicine, a Full Member of the McGill Centre for RNA Sciences, and an Associate Member of the Rosalind and Morris Goodman Cancer Institute.

Rohan Dandage
Research Associate

Aldo Hernández Corchado
Research Assistant

Hamed Heydari
Postdoctoral Researcher

Rached Alkallas
Ph.D. Student
(joint with Ian R. Watson)

Ariel Madrigal
Ph.D. Student

Zohreh Mehrjoo
Ph.D. Student
(joint with Yasser Riazalhosseini)

Octavia Dancu
Ph.D. Student

Ali Saberi
Ph.D. Student
(joint with Amin Emad)

Jing Zhao
Ph.D. Student
(joint with Yasser Riazalhosseini)

Amirhossein Zarezadeh
Ph.D. student

Ali Poursina
M.Sc. Student

Arsham Mikaeili
M.Sc. Student
(joint with Yasser Riazalhosseini)

Shivang Mistry
Undergraduate Research Intern

Jichen Wang
QLS Rotation Student

 

 

FORMER LAB MEMBERS

 

Fatima Zohra Smaili, PhD
- Position in the CSG lab: Postdoctoral Researcher
- Current position: Data Scientist, Data Sciences Montreal, Canada

Siyu Chen, PhD
- Position in the CSG lab: Postdoctoral Researcher
- Current position: Postdoctoral Scholar, UC San Francisco, USA

Gabrielle Perron, PhD
- Position in the CSG lab: Ph.D. Student
- Current position: Computational Biology Scientist, Exai Bio, USA

Wenmin Zhang, PhD
- Position in the CSG lab: PhD Student
- Current position: Postdoctoral Researcher, Montreal Heart Institute, Canada

Pubudu Nawarathna
- Position in the CSG lab: M.Sc. Student
- Current position: Bioinformatician, CellCarta

Larry Dong
- Position in the CSG lab: Undergraduate Research Assistant
- Current position: Graduate student, University of Toronto, Canada

Senthil Kailasam
- Position in the CSG lab: Postdoctoral Researcher
- Current position: Bioinformatics Specialist, Canadian Centre for Computational Genomics, Canada

Mehryar Keshavarz
- Position in the CSG lab: Research Intern
- Current position: Software Developer, Google, Canada

Nathalie Neriec
- Position in the CSG lab: Visiting Research Scholar
- Current position: Business Development Specialist, Mitacs, Canada

Larisa M. Soto
- Position in the CSG lab: M.Sc. Student
- Current position: Bioinformatics Scientist, Harvard Medical School, USA

Berat Dogan
- Position in the CSG lab: Postdoctoral Fellow
- Current position: Associate Professor, İnönü University, Turkey

Rick Farouni
- Position in the CSG lab: Postdoctoral Fellow
- Current position: Bioinformatics Scientist, ETH Zürich, Switzerland

Krishiv Shah
- Position in the CSG lab: B.Sc. Honours Student (Biology)
- Current position: Senior Consulting Analyst, Huron Consulting Group, Canada

Tianyuan Lu
- Position in the CSG lab: Graduate Research Assistant
- Current position: Assistant Professor, University of Wisconsin–Madison, USA

Michael Apostolides
- Position in the CSG lab: M.Sc. Student
- Current position: Bioinformatician, Lady Davis Institute, Montreal, Canada

Ali Nehme
- Position in the CSG lab: Postdoctoral Fellow
- Current position: Senior Analytics Consultant, Revvity Signals

Colleen Rollins
- Position in the CSG lab: Undergraduate Research Assistant
- Current position: Editorial and Project Manager, Ecopsychepedia


AVAILABLE POSITIONS

GRADUATE STUDENT

Prospective graduate students interested in joining the CSG lab 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 gene regulation, transcriptomics, 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 Genome Centre
740 Dr. Penfield Avenue, Room 7202
Montréal, Québec, H3A 0G1, Canada

CONTACT

Office: (514) 398-5308
Email: hamed.najafabadi@mcgill.ca

LINKS


Our GitHub page