Smita Krishnaswamy

Leandros Tassiulas

Menglin Yang 0001

Rex Ying

2025-05-29

ArXiv (preprint)

ImmunoStruct: a multimodal neural network framework for immunogenicity prediction from peptide-MHC sequence, structure, and biochemical properties

Kevin Bijan Givechian

João Felipe Rocha

Edward Yang

Chen Liu

Kerrie Greene

Rex Ying

Etienne Caron

Akiko Iwasaki

2025-05-20

Research Square (published)

Recovering undersampled single-cell transcriptomes with HyperCell

Emmanuel Noutahi

Alisandra K. Denton

Joseph E. Powell

Guy Wolf

Danilo Bzdok

Abstract

Single-cell transcriptomic technology has now matured, allowing quantification of mRNA transcripts corres… (see more)ponding to tens of thousands of genes within a cell. However, still only a small fraction of these mRNA is captured and measured by today’s single-cell assays. There are likely hundreds of thousands of mRNA copies present within a typical human cell, yet these assays omit a majority of the transcripts that are actually present. This introduces technical noise, especially non-biological variability and excessive sparsity, which frustrates downstream analysis and potentially skews biological conclusions. To overcome these challenges, we here develop HyperCell, a probabilistic deep learning approach that explicitly models this undersampling to produce estimates of each cell’s original gene transcript abundances across the whole transcriptome. We demonstrate that our framework offers benefits in various mRNA modeling settings, by i) correctly differentiating between spurious sampling-induced and real biological zeros, outperforming existing approaches, ii) estimating the total mRNA content of cells across states to reduce contamination due to background transcripts, iii) reducing contamination due to background transcripts, and iv) helping to counteract biases that may appear during typical differential gene expression analyses using widespread normalization approaches. Our approach to correcting for the technical noise introduced by the single-cell experimental process brings us closer to studying biology, starting from the true transcriptome of cells.

2025-04-22

Research Square (preprint)

Deep Learning Unlocks the True Potential of Organ Donation after Circulatory Death with Accurate Prediction of Time-to-Death

Xingzhi Sun

Edward De Brouwer

Chen Liu

Ramesh Batra

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Increasing the number of organ donations after circulatory death (DCD) has been identified as one of the most important ways of addressing t… (see more)he ongoing organ shortage. While recent technological advances in organ transplantation have increased their success rate, a substantial challenge in increasing the number of DCD donations resides in the uncertainty regarding the timing of cardiac death after terminal extubation, impacting the risk of prolonged ischemic organ injury, and negatively affecting post-transplant outcomes. In this study, we trained and externally validated an ODE-RNN model, which combines recurrent neural network with neural ordinary equations and excels in processing irregularly-sampled time series data. The model is designed to predict time-to-death following terminal extubation in the intensive care unit (ICU) using the last 24 hours of clinical observations. Our model was trained on a cohort of 3,238 patients from Yale New Haven Hospital, and validated on an external cohort of 1,908 patients from six hospitals across Connecticut. The model achieved accuracies of 95.3 {+/-} 1.0% and 95.4 {+/-} 0.7% for predicting whether death would occur in the first 30 and 60 minutes, respectively, with a calibration error of 0.024 {+/-} 0.009. Heart rate, respiratory rate, mean arterial blood pressure (MAP), oxygen saturation (SpO2), and Glasgow Coma Scale (GCS) scores were identified as the most important predictors. Surpassing existing clinical scores, our model sets the stage for reduced organ acquisition costs and improved post-transplant outcomes.

2025-04-18

Scientific Reports (published)

InfoGain Wavelets: Furthering the Design of Diffusion Wavelets for Graph-Structured Data

David R. Johnson

Michael Perlmutter

Diffusion wavelets extract information from graph signals at different scales of resolution by utilizing graph diffusion operators raised to… (see more) various powers, known as diffusion scales. Traditionally, the diffusion scales are chosen to be dyadic integers,

2025-04-07

ArXiv (preprint)

DiffKillR: Killing and Recreating Diffeomorphisms for Cell Annotation in Dense Microscopy Images

Chen Liu

Danqi Liao

Alejandro Parada-Mayorga

Alejandro Ribeiro

Marcello DiStasio

The proliferation of digital microscopy images, driven by advances in automated whole slide scanning, presents significant opportunities for… (see more) biomedical research and clinical diagnostics. However, accurately annotating densely packed information in these images remains a major challenge. To address this, we introduce DiffKillR, a novel framework that reframes cell annotation as the combination of archetype matching and image registration tasks. DiffKillR employs two complementary neural networks: one that learns a diffeomorphism-invariant feature space for robust cell matching and another that computes the precise warping field between cells for annotation mapping. Using a small set of annotated archetypes, DiffKillR efficiently propagates annotations across large microscopy images, reducing the need for extensive manual labeling. More importantly, it is suitable for any type of pixel-level annotation. We will discuss the theoretical properties of DiffKillR and validate it on three microscopy tasks, demonstrating its advantages over existing supervised, semi-supervised, and unsupervised methods.

2025-04-05

ICASSP 2025 - 2025 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) (published)

Hyperedge Representations with Hypergraph Wavelets: Applications to Spatial Transcriptomics

Xingzhi Sun

Charles Xu

João Felipe Rocha

Chen Liu

Benjamin Hollander-Bodie

Laney Goldman

Marcello DiStasio

Michael Perlmutter

In many data-driven applications, higher-order relationships among multiple objects are essential in capturing complex interactions. Hypergr… (see more)aphs, which generalize graphs by allowing edges to connect any number of nodes, provide a flexible and powerful framework for modeling such higher-order relationships. In this work, we introduce hypergraph diffusion wavelets and describe their favorable spectral and spatial properties. We demonstrate their utility for biomedical discovery in spatially resolved transcriptomics by applying the method to represent disease-relevant cellular niches for Alzheimer’s disease.

2025-04-05

ICASSP 2025 - 2025 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) (published)

Latent Representation Learning for Multimodal Brain Activity Translation

Arman Afrasiyabi

Dhananjay Bhaskar

Erica Lindsey Busch

Laurent Caplette

Rahul Singh

Guillaume Lajoie

Nicholas B Turk-Browne

Neuroscience employs diverse neuroimaging techniques, each offering distinct insights into brain activity, from electrophysiological recordi… (see more)ngs such as EEG, which have high temporal resolution, to hemodynamic modalities such as fMRI, which have increased spatial precision. However, integrating these heterogeneous data sources remains a challenge, which limits a comprehensive understanding of brain function. We present the Spatiotemporal Alignment of Multimodal Brain Activity (SAMBA) framework, which bridges the spatial and temporal resolution gaps across modalities by learning a unified latent space free of modality-specific biases. SAMBA introduces a novel attention-based wavelet decomposition for spectral filtering of electrophysiological recordings, graph attention networks to model functional connectivity between functional brain units, and recurrent layers to capture temporal autocorrelations in brain signal. We show that the training of SAMBA, aside from achieving translation, also learns a rich representation of brain information processing. We showcase this classify external stimuli driving brain activity from the representation learned in hidden layers of SAMBA, paving the way for broad downstream applications in neuroscience research and clinical contexts.

2025-04-05

ICASSP 2025 - 2025 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) (published)

Principal Curvatures Estimation with Applications to Single Cell Data

Yanlei Zhang

Lydia Mezrag

Xingzhi Sun

Charles Xu

Kincaid MacDonald

Dhananjay Bhaskar

Guy Wolf

Bastian Rieck

2025-04-05

ICASSP 2025 - 2025 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP) (published)

Accelerated learning of a noninvasive human brain-computer interface via manifold geometry

Erica Lindsey Busch

E. Chandra Fincke

Guillaume Lajoie

Nicholas B Turk-Browne

2025-04-02

bioRxiv (preprint)

Deep multimodal representations and classification of first-episode psychosis via live face processing

Rahul Singh

Yanlei Zhang

Dhananjay Bhaskar

Vinod Srihari

Cenk Tek

Xian Zhang

J. Adam Noah

Joy Hirsch

Schizophrenia is a severe psychiatric disorder associated with a wide range of cognitive and neurophysiological dysfunctions and long-term s… (see more)ocial difficulties. In this paper, we test the hypothesis that integration of multiple simultaneous acquisitions of neuroimaging, behavioral, and clinical information will be better for prediction of early psychosis than unimodal recordings. We propose a novel framework to investigate the neural underpinnings of the early psychosis symptoms (that can develop into Schizophrenia with age) using multimodal acquisitions of neural and behavioral recordings including functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG), and facial features. Our data acquisition paradigm is based on live face-to-face interaction in order to study the neural correlates of social cognition in first-episode psychosis (FEP). We propose a novel deep representation learning framework, Neural-PRISM, for learning joint multimodal compressed representations combining neural as well as behavioral recordings. These learned representations are subsequently used to describe, classify, and predict the severity of early psychosis in patients, as measured by the Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores. We found that incorporating joint multimodal representations from fNIRS and EEG along with behavioral recordings enhances classification between typical controls and FEP individuals. Additionally, our results suggest that geometric and topological features such as curvatures and path signatures of the embedded trajectories of brain activity enable detection of discriminatory neural characteristics in early psychosis.

2025-02-25

Frontiers in Psychiatry (published)

HiPoNet: A Multi-View Simplicial Complex Network for High Dimensional Point-Cloud and Single-Cell Data

Siddharth Viswanath

Hiren Madhu

Dhananjay Bhaskar

Jake Kovalic

David R. Johnson

Rex Ying

Christopher Tape

Ian Adelstein

Michael Perlmutter

In this paper, we propose HiPoNet, an end-to-end differentiable neural network for regression, classification, and representation learning o… (see more)n high-dimensional point clouds. Our work is motivated by single-cell data which can have very high-dimensionality --exceeding the capabilities of existing methods for point clouds which are mostly tailored for 3D data. Moreover, modern single-cell and spatial experiments now yield entire cohorts of datasets (i.e., one data set for every patient), necessitating models that can process large, high-dimensional point-clouds at scale. Most current approaches build a single nearest-neighbor graph, discarding important geometric and topological information. In contrast, HiPoNet models the point-cloud as a set of higher-order simplicial complexes, with each particular complex being created using a reweighting of features. This method thus generates multiple constructs corresponding to different views of high-dimensional data, which in biology offers the possibility of disentangling distinct cellular processes. It then employs simplicial wavelet transforms to extract multiscale features, capturing both local and global topology from each view. We show that geometric and topological information is preserved in this framework both theoretically and empirically. We showcase the utility of HiPoNet on point-cloud level tasks, involving classification and regression of entire point-clouds in data cohorts. Experimentally, we find that HiPoNet outperforms other point-cloud and graph-based models on single-cell data. We also apply HiPoNet to spatial transcriptomics datasets using spatial coordinates as one of the views. Overall, HiPoNet offers a robust and scalable solution for high-dimensional data analysis.

2025-02-10

ArXiv (preprint)