Université de Montréal
Chercheur(e) invité(e) / Invited researcher candidate
Supervisor: Timothée Poisot
Amandine Gamble
Start: 2024-09-01
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Project

Machine Learning Enables Genome-Agnostic Classification of RNA Virus Infections from Host Transcriptomes
Sequence-targeted assays can miss novel or divergent viruses. We test whether the host transcriptome alone can classify RNA virus infections without using viral sequences. Using publicly available infections of Huh7 and Calu-3 cells with diverse negative-sense RNA viruses (e.g., H1N1, H5N1, H7N7, H7N9, EBOV, MARV, NiV, RVFV, RSV, SFSV, LASV), we evaluate two host-derived feature sets—differential gene expression and alignment-free k-mer spectra—and compare hierarchical clustering with Random Forests. Across datasets and timepoints (12–24 hpi), Random Forests accurately distinguished virus classes, including settings where unsupervised clustering merged infected with mock samples. Controls with label permutation and read shuffling established non-random performance; depleting viral reads reduced cluster separability while classification remained above chance; and enriching viral reads improved both. Influenza A infections exhibited the strongest, most distinct signatures, whereas EBOV and LASV responses were subtler yet still classifiable. These results show that host-only transcriptomics encodes virus-specific, nonlinear signals that machine learning can exploit, enabling genome-agnostic classification. This approach could aid early outbreak triage when primers fail or genomes are unknown, and complements sequence-based discovery.

Publications

1- Pathogenicity and virulence of henipaviruses
Kaza, Benjamin, Hector C. Aguilar
2023 Virulence

2- Rapid protection of nonhuman primates against Marburg virus disease using a single low-dose VSV-based vaccine
O'Donnell, Kyle L., Friederike Feldmann, Benjamin Kaza, Chad S. Clancy, Patrick W. Hanley, Paige Fletcher, Andrea Marzi
2023 eBioMedicine

3- Multivalent viral particles elicit safe and efficient immunoprotection against Nipah Hendra and Ebola viruses
Ithinji, Duncan G., David W. Buchholz, Shahrzad Ezzatpour, I. Abrrey Monreal, Yu Cong, Julie Sahler, Amandip Singh Bangar, Brian Imbiakha, Viraj Upadhye, Janie Liang, Andrew Ma, Birgit Bradel-Tretheway, Benjamin Kaza, Yao Yu Yeo, Eun Jin Choi, Gunner P. Johnston, Louis Huzella, Erin Kollins, Saurabh Dixit, Shuiqing Yu, Elena Postnikova, Victoria Ortega, Avery August, Michael R. Holbrook, Hector C. Aguilar
2022 npj Vaccines

4- SARS-CoV-2 reinfection prevents acute respiratory disease in Syrian hamsters but not replication in the upper respiratory tract
Hansen, Frederick, Kimberly Meade-White, Chad Clancy, Rebecca Rosenke, Atsushi Okumura, David W. Hawman, Friederike Feldmann, Benjamin Kaza, Michael A. Jarvis, Kyle Rosenke, Heinz Feldmann
2022 Cell Reports

5- UK B.1.1.7 (Alpha) variant exhibits increased respiratory replication and shedding in nonhuman primates
Rosenke, Kyle, Friederike Feldmann, Atsushi Okumura, Frederick Hansen, Tsing-Lee Tang-Huau, Kimberly Meade-White, Benjamin Kaza, Julie Callison, Matthew C. Lewis, Brian J. Smith, Patrick W. Hanley, Jamie Lovaglio, Michael A. Jarvis, Carl Shaia, Heinz Feldmann
2021 Emerging Microbes & Infections