Portrait of Smita Krishnaswamy

Smita Krishnaswamy

Affiliate Member
Associate Professor, Yale University
Université de Montréal
Yale
Research Topics
AI in Health
Brain-computer Interfaces
Cognitive Science
Computational Biology
Computational Neuroscience
Data Geometry
Data Science
Data Sparsity
Deep Learning
Dynamical Systems
Generative Models
Geometric Deep Learning
Graph Neural Networks
Information Theory
Manifold Learning
Molecular Modeling
Representation Learning
Spectral Learning
Website
Google Scholar
LinkedIn
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Biography

Our lab works on developing foundational mathematical machine learning and deep learning methods that incorporate graph-based learning, signal processing, information theory, data geometry and topology, optimal transport and dynamics modeling that are capable of exploratory analysis, scientific inference, interpretation and hypothesis generation big biomedical datasets ranging from single-cell data, to brain imaging, to molecular structural datasets arising from neuroscience, psychology, stem cell biology, cancer biology, healthcare, and biochemistry. Our works have been instrumental in dynamic trajectory learning from static snapshot data, data denoising, visualization, network inference, molecular structure modeling and more.

Current Students

Joao Felipe Carneiro Barbosa Rocha
Collaborating researcher - Yale University
Principal supervisor :
Guy Wolf
joaofelipe.rocha@mila.quebec
Github
Google Scholar

Publications

Embedding Signals on Graphs with Unbalanced Diffusion Earth Mover’s Distance
Alexander Tong
Guillaume Huguet
Dennis Shung
Amine Natik
Manik Kuchroo
Guillaume Lajoie
Guy Wolf
Smita Krishnaswamy
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 L(1) space, whose metric we call unbalanced diffusion earth mover’s distance (UDEMD). Next, we show how this gives distances between graph signals that are robust to noise. Finally, we apply this to organizing patients based on clinical notes, embedding cells modeled as signals on a gene graph, and organizing genes modeled as signals over a large cell graph. In each case, we show that UDEMD-based embeddings find accurate distances that are highly efficient compared to other methods.
2022-05-22
ICASSP 2022 - 2022 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) (published)
doi.org
Embedding Signals on Graphs with Unbalanced Diffusion Earth Mover's Distance
Alexander Tong
Guillaume Huguet
Dennis Shung
Amine Natik
Manik Kuchroo
Guillaume Lajoie
Guy Wolf
Smita Krishnaswamy
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
2022-04-26
IEEE International Conference on Acoustics, Speech and Signal Processing (published)
doi.org
arxiv.org
Embedding Signals on Graphs with Unbalanced Diffusion Earth Mover's Distance
Alexander Tong
Guillaume Huguet
Dennis Shung
Amine Natik
Manik Kuchroo
Guillaume Lajoie
Guy Wolf
Smita Krishnaswamy
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
2022-04-26
IEEE International Conference on Acoustics, Speech, and Signal Processing (published)
doi.org
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
Guy Wolf
Akiko Iwasaki
Smita Krishnaswamy
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.

2022-02-27
Nature Biotechnology (published)
doi.org
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
Guy Wolf
Smita Krishnaswamy
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)
doi.org
Exploring the Geometry and Topology of Neural Network Loss Landscapes
Stefan Horoi
Jessie Huang
Bastian Rieck
Guillaume Lajoie
Guy Wolf
Smita Krishnaswamy
Recent work has established clear links between the generalization performance of trained neural networks and the geometry of their loss lan… (see more)dscape near the local minima to which they converge. This suggests that qualitative and quantitative examination of the loss landscape geometry could yield insights about neural network generalization performance during training. To this end, researchers have proposed visualizing the loss landscape through the use of simple dimensionality reduction techniques. However, such visualization methods have been limited by their linear nature and only capture features in one or two dimensions, thus restricting sampling of the loss landscape to lines or planes. Here, we expand and improve upon these in three ways. First, we present a novel "jump and retrain" procedure for sampling relevant portions of the loss landscape. We show that the resulting sampled data holds more meaningful information about the network's ability to generalize. Next, we show that non-linear dimensionality reduction of the jump and retrain trajectories via PHATE, a trajectory and manifold-preserving method, allows us to visualize differences between networks that are generalizing well vs poorly. Finally, we combine PHATE trajectories with a computational homology characterization to quantify trajectory differences.
2021-12-31
International Symposium on Intelligent Data Analysis (published)
doi.org
arxiv.org
Fixing Bias in Reconstruction-Based Anomaly Detection with Lipschitz Discriminators
Alexander Tong
Guy Wolf
Smita Krishnaswamy
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)
doi.org
arxiv.org
Data-Driven Learning of Geometric Scattering Modules for GNNs
Alexander Tong
Frederick Wenkel
Kincaid MacDonald
Smita Krishnaswamy
Guy Wolf
We propose a new graph neural network (GNN) module, based on relaxations of recently proposed geometric scattering transforms, which consist… (see more) of a cascade of graph wavelet filters. Our learnable geometric scattering (LEGS) module enables adaptive tuning of the wavelets to encourage band-pass features to emerge in learned representations. The incorporation of our LEGS-module in GNNs enables the learning of longer-range graph relations compared to many popular GNNs, which often rely on encoding graph structure via smoothness or similarity between neighbors. Further, its wavelet priors result in simplified architectures with significantly fewer learned parameters compared to competing GNNs. We demonstrate the predictive performance of LEGS-based networks on graph classification benchmarks, as well as the descriptive quality of their learned features in biochemical graph data exploration tasks.
2021-10-24
PubMed Central (accepted)
doi.org
arxiv.org
Multimodal Data Visualization and Denoising with Integrated Diffusion
Manik Kuchroo
Abhinav Godavarthi
Alexander Tong
Guy Wolf
Smita Krishnaswamy
We propose a method called integrated diffusion for combining multimodal datasets, or data gathered via several different measurements on th… (see more)e same system, to create a joint data diffusion operator. As real world data suffers from both local and global noise, we introduce mechanisms to optimally calculate a diffusion operator that reflects the combined information from both modalities. We show the utility of this joint operator in data denoising, visualization and clustering, performing better than other methods to integrate and analyze multimodal data. We apply our method to multi-omic data generated from blood cells, measuring both gene expression and chromatin accessibility. Our approach better visualizes the geometry of the joint data, captures known cross-modality associations and identifies known cellular populations. More generally, integrated diffusion is broadly applicable to multimodal datasets generated in many medical and biological systems.
2021-10-24
PubMed Central (accepted)
doi.org
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
Guy Wolf
Smita Krishnaswamy
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)
doi.org
Diffusion Earth Mover's Distance and Distribution Embeddings
Alexander Tong
Guillaume Huguet
Amine Natik
Kincaid MacDonald
Manik Kuchroo
Ronald R. Coifman
Guy Wolf
Smita Krishnaswamy
We propose a new fast method of measuring distances between large numbers of related high dimensional datasets called the Diffusion Earth Mo… (see more)ver's Distance (EMD). We model the datasets as distributions supported on common data graph that is derived from the affinity matrix computed on the combined data. In such cases where the graph is a discretization of an underlying Riemannian closed manifold, we prove that Diffusion EMD is topologically equivalent to the standard EMD with a geodesic ground distance. Diffusion EMD can be computed in
2021-07-19
International Conference on Machine Learning (Spotlight)
doi.org
proceedings.mlr.press
Topological analysis of single-cell data reveals shared glial landscape of macular degeneration and neurodegenerative diseases
Manik Kuchroo
Marcello DiStasio
Eda Calapkulu
Maryam Ige
Le Zhang
Amar H. Sheth
Madhvi Menon
Yu Xing
Scott Gigante
Jessie Huang
Rahul M. Dhodapkar
Bastian Rieck
Guy Wolf
Smita Krishnaswamy
Brian P. Hafler
1 A novel topological machine learning approach applied to single-nucleus RNA sequencing from human retinas… (see more) with age-related macular degeneration identifies interacting disease phase-specific glial activation states shared with Alzheimer’s disease and multiple sclerosis. 2 Neurodegeneration occurs in a wide range of diseases, including age-related macular degeneration (AMD), Alzheimer’s disease (AD), and multiple sclerosis (MS), each with distinct inciting events. To determine whether glial transcriptional states are shared across phases of degeneration, we sequenced 50,498 nuclei from the retinas of seven AMD patients and six healthy controls, generating the first single-cell transcriptomic atlas of AMD. We identified groupings of cells implicated in disease pathogenesis by applying a novel topologically-inspired machine learning approach called ‘diffusion condensation.’ By calculating diffusion homology features and performing persistence analysis, diffusion condensation identified activated glial states enriched in the early phases of AMD, AD, and MS as well as an AMD-specific proangiogenic astrocyte state promoting pathogenic neovascularization in advanced AMD. Finally, by mapping the expression of disease-associated genes to glial states, we identified key signaling interactions creating hypotheses for therapeutic intervention. Our topological analysis identified an integrated disease-phase specific glial landscape that is shared across neurodegenerative conditions affecting the central nervous system.
2021-01-19
bioRxiv (preprint)
doi.org