Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/567669

Characterizing the epigenetic landscape of cellular populations from bulk and single-cell ATAC-seq information.

Gabitto, M. I.·Rasmussen, A.·Wapinski, O.·Allaway, K.·Carriero, N.·Fishell, G. J.·Bonneau, R.
View original source ↗Export metadata ↓

Abstract

Given its ability to map chromatin accessibility with single base pair resolution, ATAC-seq has become a leading technology to probe the epigenomic landscape of single and aggregated cells. Understanding ATAC-seq data presents distinct analysis challenges, compared to RNA-seq technologies, because of the relative sparseness of the data produced and the interaction of complex noise with multiple chromatin structure scales. Methods commonly used to analyze chromatin accessibility datasets are adapted from algorithms designed to process different experimental technologies, disregarding the statistical and biological differences intrinsic to the ATAC-seq technology. Here, we present a Bayesian statistical approach, termed ChromA, to analyze ATAC-seq data. ChromA annotates the cellular epigenetic landscape by integrating information from replicates, producing a consensus de-noised annotation of chromatin accessibility. Our method can analyze single cell ATAC-seq data, improving cell type identification and correcting many of the biases generated by the sparse sampling inherent in single cell technologies. We validate ChromA on several biological systems, including mouse and human immune cells and find it effective at recovering accessible chromatin, establishing ChromA as a top preforming general platform for mapping the chromatin landscape in different cellular populations from diverse experimental designs.

Explore related subjects

bioinformaticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Gabitto, M. I., Rasmussen, A., Wapinski, O., Allaway, K., Carriero, N., Fishell, G. J., Bonneau, R.. 2019-03-04. Characterizing the epigenetic landscape of cellular populations from bulk and single-cell ATAC-seq information.. https://doi.org/10.1101/567669

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Deducing splicing events from transcript sets with splicelogic

Long-read RNA sequencing captures a greater proportion of full-length transcripts, enabling more accurate isoform identification, discovery of novel isoforms, and more precise differential transcript usage analysis. However, comparing transcripts, whether between conditions or between sets such as novel and annotated isoforms, yields complex isoform changes that are hard to manipulate, summarize, and visualize. This is compounded by vertical integration of some tools, where downstream analysis depends on the specific output of a particular upstream tool. To address this gap, we have developed splicelogic, an R/Bioconductor package that makes transcript-set comparisons biologically interpretable by turning them into discrete splicing events, such as exon skipping, alternative splice sites, intron retention, and alternative transcription start and end sites. We designed splicelogic to integrate easily with existing RNA-seq workflows and tools. The splicelogic functions are modular, readable, and extensible, making it easy for users to adapt core logic to their own custom scientific questions or novel splicing definitions. By obtaining interpretable splicing events from transcript changes, splicelogic enables downstream analyses, including annotation of RNA-binding protein recognition sites, alongside summary statistics and visualization. The splicelogic package is publicly available and distributed through Bioconductor.

bioinformatics↗
bioRxiv2026

Contrastive Learning Improves Generalization on M2OR Olfactory Binding Dataset

Olfaction-based biosensors stand to have profound impacts in fields such as medical diagnostics, national security, and drug discovery. A promising mode of vapor phase biodetection mimics volatile organic compound-olfactory receptor (VOC-OR) interactions with target-specific protein or peptide probes; however, lack of experimental coverage remains a core bottleneck. Current computational approaches aim to improve prediction of VOC-OR binding to reduce experimental burden, and current machine learning approaches fail to demonstrate a level of generalization that addresses current engineering challenges. Here, using the Molecular to Olfactory Dataset (M2OR) and Insect Olfactory Binding Protein Database (iOBPdb) datasets, data partitioning methods and their performance are evaluated on a neural network and contrastive learning framework on such VOC-OR binding datasets, varying: model training, architecture, and structure of the input data distribution. It was found that holding out certain chemical or proteomic motifs from the training data diminished model performance with a two layer neural network model. The model was able to generalize to state of the art performance (0.88 AUCROC) on every data split by applying a contrastive learning objective defined by shared molecular constituents and a stochastic sampler. This suggests the contrastive objective provides a strong inductive bias for neural networks to predict novel VOC-OR pairs. These findings highlight that model performance on pairwise biological interaction datasets can be inflated through identity leakage from constituent overlap, and emphasize the need for more robust evaluation protocols. Furthermore, we show contrastive regularization mitigates dataset degeneracy through enforcement of compatibility in the models latent geometry that may extend to other binder target-datasets where identity leakage confounds evaluation.

bioinformatics↗
bioRxiv2026

Plate design confounds donor variation and model evaluation in single-cell perturbation screens

Single-cell screens of immune cells from many donors are used to study why individuals respond differently and to benchmark response models. Each donor-perturbation combination typically occupies one well, controls are grouped, and donors share one layout, so technical effects can look biological. Using a 90-cytokine screen, two compound screens, four cohorts and simulations, we show that well effects explain most replicate-control variation in abundant cell types, controls carry a shared offset, and identical control wells differ by hundreds of differentially expressed genes at a standard threshold, about as many as two receptor-negative proteins do. Negative controls, design-aware estimators and perturbation-specific evaluation change the interpretation of four recent analyses. A deep-learning model that scores below a perturbation-agnostic predictor under standard evaluation outperforms a simple baseline on perturbation-specific differences in two of three cell types (significantly in one with stricter controls), but predicts less well the component shared with inert wells.

bioinformatics↗