Article Computer Science, Interdisciplinary Applications
Generalized Functional Pruning Optimal Partitioning (GFPOP) for Constrained Changepoint Detection in Genomic Data
Toby Dylan Hocking, Guillem Rigaill, Paul Fearnhead, Guillaume Bourque
Summary: The algorithm utilizes constrained changepoint models for peak detection in genomic data sets and proposes a dynamic programming algorithm and sequential search algorithm, which have low computational cost and high speed.
JOURNAL OF STATISTICAL SOFTWARE (2022)
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Article Biology
Application of ATAC-Seq for genome-wide analysis of the chromatin state at single myofiber resolution
Korin Sahinyan, Darren M. Blackburn, Marie-Michelle Simon, Felicia Lazure, Tony Kwan, Guillaume Bourque, Vahab D. Soleimani, Y. M. Dennis Lo
Summary: Myofibers are versatile components of skeletal muscle, undergoing key chromatin alterations under various biological and disease conditions. Single-cell sequencing techniques offer a window into the epigenome of myonuclei, while single myofiber ATAC-Seq allows for in-depth analysis of chromatin accessibility and comparative studies between physiological and disease states. These methods reveal significant differences in chromatin regulation in muscle fibers, with implications for developmental processes and muscle-wasting diseases.
ELIFE (2022)
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Article Oncology
Glioblastoma scRNA-seq shows treatment-induced, immune-dependent increase in mesenchymal cancer cells and structural variants in distal neural stem cells
Charles P. Couturier, Javad Nadaf, Zhaorong Li, Salma Baig, Gabriele Riva, Phuong Le, Daan J. Kloosterman, Jean Monlong, Andriniaina Nkili Meyong, Redouane Allache, Theresa Degenhard, Mariam Al-Rashid, Marie-Christine Guiot, Guillaume Bourque, Jiannis Ragoussis, Leila Akkari, Francisco J. Quintana, Kevin Petrecca
Summary: Using single-cell RNA sequencing, researchers found that there are multiple neural lineages in new and recurrent glioblastoma, with an enrichment of cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. They also discovered that neural stem cells (NSCs) in the subventricular zone (SVZ) of glioblastoma patients harbored glioblastoma chromosomal anomalies and were likely the cells of origin. Additionally, they observed that radiotherapy induced similar gene signatures in mesenchymal cancer cells and TME reactive astrocytes in a myeloid-dependent manner.
NEURO-ONCOLOGY (2022)
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Article Multidisciplinary Sciences
A systems biology approach identifies candidate drugs to reduce mortality in severely ill patients with COVID-19
Vinicius M. Fava, Mathieu Bourgey, Pubudu M. Nawarathna, Marianna Orlova, Pauline Cassart, Donald C. Vinh, Matthew Pellan Cheng, Guillaume Bourque, Erwin Schurr, David Langlais
Summary: This study used a systems biology approach to investigate severely ill COVID patients and found significant differences in monocyte epigenetic and transcriptomic attributes between those who survived and those who succumbed to the disease. Messenger RNA metabolism, RNA splicing, and interferon signaling pathways were identified as key host responses associated with non-survival. Tacrolimus, zotatifin, and nintedanib were identified as strong candidate drugs for the treatment of severely ill COVID patients at the time of hospital admission.
SCIENCE ADVANCES (2022)
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Article Oncology
Intra-Tumoral CD8+T-Cell Infiltration and PD-L1 Positivity in hom*ologous Recombination Deficient Pancreatic Ductal Adenocarcinoma
Bryn Golesworthy, Yifan Wang, Amanda Tanti, Alain Pacis, Joan Miguel Romero, Adeline Cuggia, Celine Domecq, Guillaume Bourdel, Robert E. Denroche, Gun Ho Jang, Robert C. Grant, Ayelet Borgida, Barbara T. Grunwald, Anna Dodd, Julie M. Wilson, Guillaume Bourque, Grainne M. O'Kane, Sandra E. Fischer, Chelsea Maedler Kron, Pierre-Olivier Fiset, Atilla Omeroglu, William D. Foulkes, Steven Gallinger, Marie-Christine Guiot, Zu-Hua Gao, George Zogopoulos
Summary: This study investigated the immune contexture of HR-d PDAC using multiplex immunohistochemistry. The results showed higher infiltration of intra-tumoral CD8+ T-cells and increased FOXP3+ Tregs in HR-d PDAC compared to HR/MMR-intact PDAC. Additionally, PD-L1 positivity was observed in a subset of HR-d PDAC cases. These findings suggest that HR-d PDAC may be responsive to immune checkpoint inhibitor treatment strategies.
FRONTIERS IN ONCOLOGY (2022)
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Article Biochemistry & Molecular Biology
The amino acid sensor GCN2 suppresses terminal oligopyrimidine (TOP) mRNA translation via La-related 1 (LARP1)
Zeenat Farooq, Fedho Kusuma, Phillip Burke, Catherine R. Dufour, Duckgue Lee, Negar Tabatabaei, Phoenix Toboz, Ernest Radovani, Jack F. Greenblatt, Jalees Rehman, Jacob Class, Arkady Khoutorsky, Bruno D. Fonseca, Justin M. Richner, Eloi Mercier, Guillaume Bourque, Vincent Giguere, Arvind R. Subramaniam, Jaeseok Han, Soroush Tahmasebi
Summary: In this study, the researchers identify the involvement of the nutrient sensing kinase GCN2 in regulating LARP1-mediated inhibition of TOP mRNA translation. They demonstrate that GCN2 controls LARP1 activity through two mechanisms: ATF4-dependent transcriptional induction of LARP1 mRNA and GCN1-mediated recruitment of LARP1 to stalled ribosomes. These findings provide new insights into the regulation of TOP mRNA translation and shed light on the role of GCN2 in this process.
JOURNAL OF BIOLOGICAL CHEMISTRY (2022)
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Article Genetics & Heredity
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
Guillaume Butler-Laporte, Gundula Povysil, Jack A. Kosmicki, Elizabeth T. Cirulli, Theodore Drivas, Simone Furini, Chadi Saad, Axel Schmidt, Pawel Olszewski, Urszula Korotko, Mathieu Quinodoz, Elifnaz Celik, Kousik Kundu, Klaudia Walter, Junghyun Jung, Amy D. Stockwell, Laura G. Sloofman, Daniel M. Jordan, Ryan C. Thompson, Diane Del Valle, Nicole Simons, Esther Cheng, Robert Sebra, Eric E. Schadt, Seunghee Kim-Schulze, Sacha Gnjatic, Miriam Merad, Joseph D. Buxbaum, Noam D. Beckmann, Alexander W. Charney, Bartlomiej Przychodzen, Timothy Chang, Tess D. Pottinger, Ning Shang, Fabian Brand, Francesca Fava, Francesca Mari, Karolina Chwialkowska, Magdalena Niemira, Szymon Pula, J. Kenneth Baillie, Alex Stuckey, Antonio Salas, Xabier Bello, Jacobo Pardo-Seco, Alberto Gomez-Carballa, Irene Rivero-Calle, Federico Martinon-Torres, Andrea Ganna, Konrad J. Karczewski, Kumar Veerapen, Mathieu Bourgey, Guillaume Bourque, Robert Jm Eveleigh, Vincenzo Forgetta, David Morrison, David Langlais, Mark Lathrop, Vincent Mooser, Tomoko Nakanishi, Robert Frithiof, Michael Hultstrom, Miklos Lipcsey, Yanara Marincevic-Zuniga, Jessica Nordlund, Kelly M. Schiabor Barrett, William Lee, Alexandre Bolze, Simon White, Stephen Riffle, Francisco Tanudjaja, Efren Sandoval, Iva Neveux, Shaun Dabe, Nicolas Casadei, Susanne Motameny, Manal Alaamery, Salam Massadeh, Nora Aljawini, Mansour S. Almutairi, Yaseen M. Arabi, Saleh A. Alqahtani, Fawz S. Al Harthi, Amal Almutairi, Fatima Alqubaishi, Sarah Alotaibi, Albandari Binowayn, Ebtehal A. Alsolm, Hadeel El Bardisy, Mohammad Fawzy, Fang Cai, Nicole Soranzo, Adam Butterworth, Daniel H. Geschwind, Stephanie Arteaga, Alexis Stephens, Manish J. Butte, Paul C. Boutros, Takafumi N. Yamaguchi, Shu Tao, Stefan Eng, Timothy Sanders, Paul J. Tung, Michael E. Broudy, Yu Pan, Alfredo Gonzalez, Nikhil Chavan, Ruth Johnson, Bogdan Pasaniuc, Brian Yaspan, Sandra Smieszek, Carlo Rivolta, Stephanie Bibert, Pierre-Yves Bochud, Maciej Dabrowski, Pawel Zawadzki, Mateusz Sypniewski, Elzbieta Kaja, Pajaree Chariyavilaskul, Voraphoj Nilaratanakul, Nattiya Hirankarn, Vorasuk Shotelersuk, Monnat Pongpanich, Chureerat Phokaew, Wanna Chetruengchai, Katsushi Tokunaga, Masaya Sugiyama, Yosuke Kawai, Takanori Hasegawa, Tatsuhiko Naito, Ho Namkoong, Ryuya Edahiro, Akinori Kimura, Seishi Ogawa, Takanori Kanai, Koichi f*ckunaga, Yukinori Okada, Seiya Imoto, Satoru Miyano, Serghei Mangul, Malak S. Abedalthagafi, Hugo Zeberg, Joseph J. Grzymski, Nicole L. Washington, Stephan Ossowski, Kerstin U. Ludwig, Eva C. Schulte, Olaf Riess, Marcin Moniuszko, Miroslaw Kwasniewski, Hamdi Mbarek, Said I. Ismail, Anurag Verma, David B. Goldstein, Krzysztof Kiryluk, Alessandra Renieri, Manuel A. R. Ferreira, J. Brent Richards
Summary: Host genetics play a crucial role in COVID-19 outcomes, and studying rare variants can provide additional insights. A study combining whole-exome and whole-genome sequencing from 21 cohorts across 12 countries found that carrying a rare deleterious variant in the TLR7 gene on chromosome X is associated with a 5.3-fold increase in severe disease. This association is consistent across genders, further supporting TLR7 as a genetic determinant of severe COVID-19.
PLOS GENETICS (2022)
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Article Biochemistry & Molecular Biology
Genetic variation in the Y chromosome and sex-biased DNA methylation in somatic cells in the mouse
Enkhjin Batdorj, Najla AlOgayil, Qinwei Kim-Wee Zhuang, Jose Hector Galvez, Klara Bauermeister, Kei Nagata, Tohru Kimura, Monika A. Ward, Teruko Taketo, Guillaume Bourque, Anna K. Naumova
Summary: Several lines of evidence suggest that the presence of the Y chromosome influences DNA methylation of autosomal loci. In this study, we identified Y chromosome dependent differentially methylated regions (yDMRs) in mice and found that most of the yDMRs were located in transposable elements (TEs) and had lower methylation in XY mice compared to XX or XO mice. Further analyses showed that genetic variation in the Y chromosome influenced methylation levels of autosomal regions.
MAMMALIAN GENOME (2023)
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Article Cell Biology
Identification of R-Spondin Gene Signature Predictive of Metastatic Progression in BRAFV600E-Positive Papillary Thyroid Cancer
Sabrina Daniela da Silva, Gregoire B. Morand, Luciana Diesel, Jefferson Muniz de Lima, Krikor Bijian, Senthilkumar Kailasam, Francois Lefebvre, Guillaume Bourque, Michael Hier, Moulay A. Alaoui-Jamali
Summary: In this study, a high-throughput RNA sequencing technology was used to investigate a group of papillary thyroid carcinomas (PTCs) with an unusually aggressive phenotype. It was found that metastatic PTCs with mutated BRAF (V600E) expressed an up-regulation of RSPO4 and genes involved in focal adhesion and cell-extracellular matrix signaling. Further validation confirmed the upregulation of these target genes in metastatic PTC cases. Preclinical studies supported the association between RSPO4 overexpression and BRAF V600E mutation, indicating the potential for co-targeting B-Raf, RSPO, and focal adhesion proteins as a pharmacological approach for aggressive BRAF V600E PTC.
CELLS (2023)
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Article Biochemistry & Molecular Biology
ZMYM2 is essential for methylation of germline genes and active transposons in embryonic development
Adda-Lee Graham-Paquin, Deepak Saini, Jacinthe Sirois, Ishtiaque Hossain, Megan S. Katz, Qinwei Kim-Wee Zhuang, Sin Young Kwon, Yojiro Yamanaka, Guillaume Bourque, Maxime Bouchard, William A. Pastor
Summary: Zmym2(-/-) mice exhibit embryonic lethality and fail to undergo proper DNA methylation, resulting in upregulation of germline genes and abnormal expression of transposon-gene fusion transcripts. It suggests that ZMYM2 plays a crucial role in early embryonic development and DNA methylation patterning.
NUCLEIC ACIDS RESEARCH (2023)
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Article Biochemical Research Methods
RNAget: an API to securely retrieve RNA quantifications
Sean Upchurch, Emilio Palumbo, Jeremy Adams, David Bujold, Guillaume Bourque, Jared Nedzel, Keenan Graham, Meenakshi S. Kagda, Pedro Assis, Benjamin Hitz, Emilio Righi, Roderic Guigo, Barbara J. Wold
Summary: Large-scale sharing of genomic quantification data requires standardized access interfaces. In this project, RNAget, an API for secure access to genomic quantification data in matrix form, was developed. RNAget allows for slicing matrices to extract desired subsets of data and can be applied to various expression matrix-format data, including RNA sequencing and microarrays. It can also be extended to other sequence-based genomics quantification matrices such as ATAC-seq and ChIP-seq.
BIOINFORMATICS (2023)
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Article Cell Biology
Genome graphs detect human polymorphisms in active epigenomic state during influenza infection
Cristian Groza, Xun Chen, Alain Pacis, Marie-Michelle Simon, Albena Pramatarova, Katherine A. Aracena, Tomi Pastinen, Luis B. Barreiro, Guillaume Bourque
Summary: This study demonstrates that genome graphs can reveal regulatory regions that would have been overlooked by other approaches, providing important insights into the impact of genetic variants on processes such as immunity.
CELL GENOMICS (2023)
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Meeting Abstract Oncology
Identifying genetic vulnerabilities of chromosome 4p large copy number variants in triple negative breast cancer
Michael Schwartz, Rohan Dandage, Lynn Karam, Alain Pacis, Hellen Kuasne, Anne-Marie Fortier, Sidong Huang, Guillaume Bourque, Traver Hart, Elena Kuzmin, Morag Park
CANCER RESEARCH (2022)
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Meeting Abstract Oncology
Evolution of large copy number variants in breast cancer through genetic network rewiring
Elena Kuzmin, Jean Monlong, Mathieu Bourgey, Jarry Barber, Tom Lesluyes, Toby Baker, Genevieve Morin, Dongmei Zou, Michael Schwartz, Yang Yang, Alain Pacis, Constanza Martinez, Hellen Kuasne, Anne-Marie Fortier, Rui Li, Claudia Kleinman, Sidong Huang, Peter van Loo, Quaid Morris, Jiannis Ragoussis, Guillaume Bourque, Morag Park
CANCER RESEARCH (2022)
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Meeting Abstract Oncology
Genomic classification to refine prognosis in clear cell renal cell carcinoma.
Kate I. Glennon, Naveen S. Vasudev, Ghislaine Scelo, Michelle Wilson, Louis Letourneau, Robert Eveleigh, Nazanin Nourbehesht, Madeleine Arseneault, Antoine Paccard, Lars Egevad, Juris Viksna, Edgars Celms, Sharon M. Jackson, Behnoush Abedi-Ardekani, Anne Y. Warren, Peter J. Selby, Sebastian Trainor, Michael Kimuli, Naeem Soomro, Adebanji Adeyoju, Poulam Patel, Magdalena B. Wozniak, Ivana Holcatova, Antonin Brisuda, Vladimir Janout, Estelle Chanudet, David Zaridze, Anush Moukeria, Oxana Shangina, Lenka Foretova, Marie Navratilova, Dana Mates, Viorel Jinga, Ljiljana Bogdanovic, Bozidar Kovacevic, Anne Cambon-Thomsen, Guillaume Bourque, Alvis Brazma, Jorg Tost, Paul Brennan, Mark Lathrop, Yasser Riazalhosseini, Rosamonde E. Banks
CANCER RESEARCH (2022)
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