Mathieu Blanchette

Lucas Nelson

Maîtrise recherche - McGill

Adam Stecklov

Maîtrise recherche - McGill

César Miguel Valdez Cordova

Doctorat - McGill

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Nicole Zhang

Doctorat - McGill

Co-superviseur⋅e :

Yoshua Bengio

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Yijie Zhang

Doctorat - McGill

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Publications

Reconstruction of full-length LINE-1 progenitors from ancestral genomes

Laura F Campitelli

Isaac Yellan

Mihai Albu

Marjan Barazandeh

Zain M Patel

Timothy R Hughes

2022-05-12

Genetics (publié)

Reconstruction of full-length LINE-1 progenitors from ancestral genomes

Laura F. Campitelli

Isaac Yellan

Mihai Tudor Albu

Marjan Barazandeh

Zain M. Patel

T. Hughes

Abstract Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, wit… (voir plus)h 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily. Here, we have coupled 2 levels of sequence reconstruction (at the level of whole genomes and L1 subfamilies) to reconstruct progenitor sequences for all human L1 subfamilies that are more functionally and phylogenetically plausible than existing models. Most of the reconstructed sequences are at or near the canonical length of L1s and encode uninterrupted ORFs with expected protein domains. We also show that the presence or absence of binding sites for KRAB-C2H2 Zinc Finger Proteins, even in ancient-reconstructed progenitor L1s, mirrors binding observed in human ChIP-exo experiments, thus extending the arms race and domestication model. RepeatMasker searches of the modern human genome suggest that the new models may be able to assign subfamily resolution identities to previously ambiguous L1 instances. The reconstructed L1 sequences will be useful for genome annotation and functional study of both L1 evolution and L1 contributions to host regulatory networks.

2022-05-12

Genetics (published)

Phylogenetic Manifold Regularization: A semi-supervised approach to predict transcription factor binding sites

Faizy Ahsan

Alexandre Drouin

Franccois Laviolette

Doina Precup

The computational prediction of transcription factor binding sites remains a challenging problems in bioinformatics, despite significant met… (voir plus)hodological developments from the field of machine learning. Such computational models are essential to help interpret the non-coding portion of human genomes, and to learn more about the regulatory mechanisms controlling gene expression. In parallel, massive genome sequencing efforts have produced assembled genomes for hundred of vertebrate species, but this data is underused. We present PhyloReg, a new semi-supervised learning approach that can be used for a wide variety of sequence-to-function prediction problems, and that takes advantage of hundreds of millions of years of evolution to regularize predictors and improve accuracy. We demonstrate that PhyloReg can be used to better train a previously proposed deep learning model of transcription factor binding. Simulation studies further help delineate the benefits of the a pproach. G ains in prediction accuracy are obtained over a broad set of transcription factors and cell types.

2020-12-16

2020 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) (publié)

Algorithms in Bioinformatics

P. Agarwal

Tatsuya Akutsu

Amir Amihood

Alberto Apostolico

C. Benham

Gary Gustaf Benson

Nadia El-Mabrouk

Olivier Gascuel

Raffaele Giancarlo

R. Guigó

Michael Hallet

D. Huson

G. Kucherov

Michelle R. Lacey

Jens Lagergren

Giuseppe Lancia

Gad M. Landau

Thierry. Lecroq

B. Moret … (voir 21 de plus)

S. Morishita

Elchanan Mossel

Vincent Moulton

Lior S. Pachter

Knut Reinert

I. Rigoutsos

David Sankoff

Sophie Schbath

Eran Segal

Charles Semple

J. Setubal

Roded Sharan

S. Skiena

Jens Stoye

Esko Ukkonen

Lisa Allen Vawter

Alfonso Valencia

Tandy J. Warnow

Lusheng Wang

Rita Casadio

Gene Myers

2012-10-01

Lecture Notes in Computer Science (publié)