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

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

Collaborating researcher - Yale University
Principal supervisor :

Publications

Topological Analysis of Single-Cell Hierarchy Reveals Inflammatory Glial Landscape of Macular Degeneration
Manik Kuchroo
Marcello DiStasio
Eric Song
Eda Calapkulu
Maryam Ige
Amar H. Sheth
Madhvi Menon
Abhinav Godavarthi
Yu Xing
Scott Gigante
Holly Steach
Janhavi Narain
George Mourgkos
Rahul M. Dhodapkar
Matthew J. Hirn
Bastian Rieck … (see 3 more)
Brian P. Hafler
Topological Analysis of Single-Cell Hierarchy Reveals Inflammatory Glial Landscape of Macular Degeneration
Manik Kuchroo
Marcello DiStasio
Eric Song
Eda Calapkulu
Maryam Ige
Amar H. Sheth
Madhvi Menon
Abhinav Godavarthi
Yu Xing
Scott Gigante
Holly Steach
Janhavi Narain
George Mourgkos
Rahul M. Dhodapkar
Matthew J. Hirn
Bastian Rieck … (see 3 more)
Brian P. Hafler
Uncovering the Folding Landscape of RNA Secondary Structure Using Deep Graph Embeddings
Egbert Castro
Andrew Benz
Biomolecular graph analysis has recently gained much attention in the emerging field of geometric deep learning. Here we focus on organizing… (see more) biomolecular graphs in ways that expose meaningful relations and variations between them. We propose a geometric scattering autoencoder (GSAE) network for learning such graph embeddings. Our embedding network first extracts rich graph features using the recently proposed geometric scattering transform. Then, it leverages a semi-supervised variational autoencoder to extract a low-dimensional embedding that retains the information in these features that enable prediction of molecular properties as well as characterize graphs. We show that GSAE organizes RNA graphs both by structure and energy, accurately reflecting bistable RNA structures. Also, the model is generative and can sample new folding trajectories.
Uncovering the Topology of Time-Varying fMRI Data using Cubical Persistence
Bastian Rieck
Tristan Yates
Christian Bock
Karsten Borgwardt
Nicholas Turk-Browne
Functional magnetic resonance imaging (fMRI) is a crucial technology for gaining insights into cognitive processes in humans. Data amassed f… (see more)rom fMRI measurements result in volumetric data sets that vary over time. However, analysing such data presents a challenge due to the large degree of noise and person-to-person variation in how information is represented in the brain. To address this challenge, we present a novel topological approach that encodes each time point in an fMRI data set as a persistence diagram of topological features, i.e. high-dimensional voids present in the data. This representation naturally does not rely on voxel-by-voxel correspondence and is robust to noise. We show that these time-varying persistence diagrams can be clustered to find meaningful groupings between participants, and that they are also useful in studying within-subject brain state trajectories of subjects performing a particular task. Here, we apply both clustering and trajectory analysis techniques to a group of participants watching the movie 'Partly Cloudy'. We observe significant differences in both brain state trajectories and overall topological activity between adults and children watching the same movie.
Multiscale PHATE Exploration of SARS-CoV-2 Data Reveals Multimodal Signatures of Disease
Manik Kuchroo
Patrick Wong
Jean-Christophe Grenier
Dennis Shung
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
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.

Learning General Transformations of Data for Out-of-Sample Extensions
Matthew Amodio
David van Dijk
While generative models such as GANs have been successful at mapping from noise to specific distributions of data, or more generally from on… (see more)e distribution of data to another, they cannot isolate the transformation that is occurring and apply it to a new distribution not seen in training. Thus, they memorize the domain of the transformation, and cannot generalize the transformation out of sample. To address this, we propose a new neural network called a Neuron Transformation Network (NTNet) that isolates the signal representing the transformation itself from the other signals representing internal distribution variation. This signal can then be removed from a new dataset distributed differently from the original one trained on. We demonstrate the effectiveness of our NTNet on more than a dozen synthetic and biomedical single-cell RNA sequencing datasets, where the NTNet is able to learn the data transformation performed by genetic and drug perturbations on one sample of cells and successfully apply it to another sample of cells to predict treatment outcome.
TrajectoryNet: A Dynamic Optimal Transport Network for Modeling Cellular Dynamics
It is increasingly common to encounter data from dynamic processes captured by static cross-sectional measurements over time, particularly i… (see more)n biomedical settings. Recent attempts to model individual trajectories from this data use optimal transport to create pairwise matchings between time points. However, these methods cannot model continuous dynamics and non-linear paths that entities can take in these systems. To address this issue, we establish a link between continuous normalizing flows and dynamic optimal transport, that allows us to model the expected paths of points over time. Continuous normalizing flows are generally under constrained, as they are allowed to take an arbitrary path from the source to the target distribution. We present TrajectoryNet, which controls the continuous paths taken between distributions to produce dynamic optimal transport. We show how this is particularly applicable for studying cellular dynamics in data from single-cell RNA sequencing (scRNA-seq) technologies, and that TrajectoryNet improves upon recently proposed static optimal transport-based models that can be used for interpolating cellular distributions.
Image-to-image Mapping with Many Domains by Sparse Attribute Transfer
Visualizing structure and transitions in high-dimensional biological data
Kevin R. Moon
David van Dijk
Zheng Wang
Scott Gigante
Daniel B. Burkhardt
William S. Chen
Kristina Yim
Antonia van den Elzen
Matthew Hirn
Ronald R. Coifman
Natalia Ivanova
Author Correction: Visualizing structure and transitions in high-dimensional biological data
Kevin R. Moon
David van Dijk
Zheng Wang
Scott Gigante
Daniel B. Burkhardt
William S. Chen
Kristina Yim
Antonia van den Elzen
Matthew Hirn
Ronald R. Coifman
Natalia Ivanova
Tess C. Branon
Justin A. Bosch
Ariana D. Sanchez
Namrata D. Udeshi
Tanya Svinkina
Steven A. Carr
Jessica L. Feldman … (see 2 more)
Norbert Perrimon
Alice Y. Ting