Smita Krishnaswamy

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Publications

Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages

Fatima Mostefai

Isabel Gamache

Arnaud N'Guessan

Justin Pelletier

Jessie Huang

Carmen Lia Murall

Ahmad Pesaranghader

Vanda Gaonac’h-Lovejoy

David J. Hamelin

Raphaël Poujol

Jean-Christophe Grenier

Martin Smith

Etienne Caron

Morgan Craig

B. Jesse Shapiro

Julie G. Hussin

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19)… (see more), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.

2022-02-20

Frontiers in Medicine (published)

Fixing Bias in Reconstruction-Based Anomaly Detection with Lipschitz Discriminators

Alexander Tong

Anomaly detection is of great interest in fields where abnormalities need to be identified and corrected (e.g., medicine and finance). Deep … (see more)learning methods for this task often rely on autoencoder reconstruction error, sometimes in conjunction with other errors. We show that this approach exhibits intrinsic biases that lead to undesirable results. Reconstruction-based methods are sensitive to training-data outliers and simple-to-reconstruct points. Instead, we introduce a new unsupervised Lipschitz anomaly discriminator that does not suffer from these biases. Our anomaly discriminator is trained, similar to the ones used in GANs, to detect the difference between the training data and corruptions of the training data. We show that this procedure successfully detects unseen anomalies with guarantees on those that have a certain Wasserstein distance from the data or corrupted training set. These additions allow us to show improved performance on MNIST, CIFAR10, and health record data.

2021-11-27

Journal of Signal Processing Systems (unknown)

arxiv.org

Data-driven approaches for genetic characterization of SARS-CoV-2 lineages

Fatima Mostefai

Isabel Gamache

Jessie Huang

Arnaud N’Guessan

Justin Pelletier

Ahmad Pesaranghader

David Hamelin

Carmen Lia Murall

Raphaël Poujol

Jean-Christophe Grenier

Martin Smith

Etienne Caron

Morgan Craig

Jesse Shapiro

Julie G. Hussin

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19)… (see more), has been sequenced at an unprecedented scale, leading to a tremendous amount of viral genome sequencing data. To understand the evolution of this virus in humans, and to assist in tracing infection pathways and designing preventive strategies, we present a set of computational tools that span phylogenomics, population genetics and machine learning approaches. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic, using 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets, enabling real-time analyses. Furthermore, time series change of Tajima’s D provides a powerful metric of population expansion. Unsupervised learning techniques further highlight key steps in variant detection and facilitate the study of the role of this genomic variation in the context of SARS-CoV-2 infection, with Multiscale PHATE methodology identifying fine-scale structure in the SARS-CoV-2 genetic data that underlies the emergence of key lineages. The computational framework presented here is useful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of worldwide populations of humans and other organisms.

2021-09-28

BioRxiv (preprint)

Embedding Signals on Graphs with Unbalanced Diffusion Earth Mover's Distance

Dennis Shung

Manik Kuchroo

In modern relational machine learning it is common to encounter large graphs that arise via interactions or similarities between observation… (see more)s in many domains. Further, in many cases the target entities for analysis are actually signals on such graphs. We propose to compare and organize such datasets of graph signals by using an earth mover's distance (EMD) with a geodesic cost over the underlying graph. Typically, EMD is computed by optimizing over the cost of transporting one probability distribution to another over an underlying metric space. However, this is inefficient when computing the EMD between many signals. Here, we propose an unbalanced graph EMD that efficiently embeds the unbalanced EMD on an underlying graph into an

2020-12-31

arXiv.org (preprint)

arxiv.org

Multiscale PHATE Exploration of SARS-CoV-2 Data Reveals Multimodal Signatures of Disease

Manik Kuchroo

Jessie Huang

Patrick Wong

Jean-Christophe Grenier

Dennis Shung

Alexander Tong

Carolina Lucas

Jon Klein

Daniel B. Burkhardt

Scott Gigante

Abhinav Godavarthi

Benjamin Israelow

Tianyang Mao

Ji Eun Oh

Julio Silva

Takehiro Takahashi

Camila D. Odio

Arnau Casanovas-Massana

John Fournier

Shelli Farhadian … (see 7 more)

Charles S. Dela Cruz

Albert I. Ko

F. Perry Wilson

Julie Hussin

Akiko Iwasaki

Abstract

The biomedical community is producing increasingly high dimensional datasets, integrated from hundreds of… (see more) patient samples, which current computational techniques struggle to explore. To uncover biological meaning from these complex datasets, we present an approach called Multiscale PHATE, which learns abstracted biological features from data that can be directly predictive of disease. Built on a coarse graining process called diffusion condensation, Multiscale PHATE learns a data topology that can be analyzed at coarse levels for high level summarizations of data, as well as at fine levels for detailed representations on subsets. We apply Multiscale PHATE to study the immune response to COVID-19 in 54 million cells from 168 hospitalized patients. Through our analysis of patient samples, we identify CD16-hi,CD66b-lo neutrophil and IFNγ+,GranzymeB+ Th17 cell responses enriched in patients who die. Furthermore, we show that population groupings Multiscale PHATE discovers can be directly fed into a classifier to predict disease outcome. We also use Multiscale PHATE-derived features to construct two different manifolds of patients, one from abstracted flow cytometry features and another directly on patient clinical features, both associating immune subsets and clinical markers with outcome.

2020-11-16

bioRxiv (preprint)