Scholars@Duke
Rohit Singh

Scholarly Works - Preprints

COMPASS: Component-Wise Inference of Shared and Gene-Specific Perturbation Response

Preprint · August 6, 2026 Predicting how a genetic perturbation reshapes a cell's transcriptome is a central goal of computational biology. Previous studies report that the mean response across training perturbations rivals specialized models on standard accuracy metrics, e ... Full text Cite

Learning a PRECISE language for small-molecule binding

Preprint · 2026 Virtual screening of billion-scale compound libraries has become feasible through machine learning approaches. In particular, CoNCISE (RECOMB 2025) introduced drug quantization via code-books, achieving highly scalable and accurate binary predictions. Howe ... Full text Cite

EvoPool: Evolution-Guided Pooling of Protein Language Model Embeddings

Preprint · 2026 Protein language models (PLMs) encode amino acid sequences into residue-level embeddings that must be pooled into fixed-size representations for downstream protein-level prediction tasks. Although these embeddings implicitly reflect evolutionary constraint ... Full text Cite

DeltaNMF: A Two-Stage Neural NMF for Differential Gene Program Discovery

Preprint · 2026 Non-negative matrix factorization (NMF) is a foundational dimensionality-reduction method in single-cell transcriptomics, valued for its interpretable gene programs. However, in case-control settings common in perturbation and disease research, standard NM ... Full text Cite

TP53-mediated bidirectional lineage plasticity drives alveolar epithelial cell extrusion and tissue remodeling

Preprint · 2026 Cell extrusion contributes to epithelial homeostasis, but its dysregulation can lead to tumorigenesis or degeneration. A fine balance in this process is therefore essential for tissue integrity. Yet the cell types and states vulnerable to extrusion, and th ... Full text Cite

Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing.

Preprint · May 27, 2025 The syncytiotrophoblast (STB) is a multinucleated cell layer that forms the outer surface of human chorionic villi. Its unusual structure, with billions of nuclei in a single cell, makes it difficult to resolve using conventional single-cell methods. To be ... Full text Link to item Cite

Tracing the Shared Foundations of Gene Expression and Chromatin Structure.

Preprint · April 2, 2025 UNLABELLED: The three-dimensional organization of chromatin into topologically associating domains (TADs) may impact gene regulation by bringing distant genes into contact. However, many questions about TADs' function and their influence on transcription r ... Full text Link to item Cite

Learning a CoNCISE language for small-molecule binding

Preprint · 2025 Rapid advances in deep learning have improved in silico methods for drug-target interaction (DTI) prediction. However, current methods do not scale to the massive catalogs that list millions or billions of commercially-available small molecules. Here, we ... Full text Cite

SAME: Topology-flexible transforms enable robust integration of multimodal spatial omics

Preprint · 2025 Spatial omics technologies provide complementary and layered molecular insights that span proteins, transcripts, and metabolites. However, aligning and integrating these modalities across serial tissue sections remains a computational challenge. Existing a ... Full text Cite

USHER: Guiding Foundation Model Representations through Distribution Shifts

Preprint · 2025 Foundation models pre-trained on certain biological data modalities exhibit systematic representational biases when encountering out-of-distribution (OOD) data from new assays. The embedding drift largely arises from instrumentation and protocol-related ar ... Full text Cite

Topology-Driven Discovery of Transmembrane Protein S-Palmitoylation.

Preprint · September 8, 2024 Protein S-palmitoylation is a reversible lipophilic posttranslational modification regulating a diverse number of signaling pathways. Within transmembrane proteins (TMPs), S-palmitoylation is implicated in conditions from inflammatory disorders to respirat ... Full text Link to item Cite

Miniaturizing, Modifying, and Magnifying Nature’s Proteins with Raygun

Preprint · 2024 Proteins have evolved over billions of years through extensive and coordinated substitutions, insertions and deletions (indels). Computational protein design cannot yet fully mimic nature’s ability to engineer new proteins from existing templates. Protein ... Full text Cite

Local transcriptional covariation produces accurate estimates of cell phenotype

Preprint · 2023 The utility of single-cell RNA sequencing (scRNA-seq) is premised on the notion that transcriptional state can faithfully reflect cell phenotype. However, scRNA-seq measurements are noisy and sparse, with individual transcript counts showing limited correl ... Full text Cite

Deciphering the species-level structure of topologically associating domains

Preprint · 2021 Summary Chromosome conformation capture technologies such as Hi-C have revealed a rich hierarchical structure of chromatin, with topologically associating domains (TADs) as a key organizational unit, but experimentally reported TAD architectures, ... Full text Cite