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Results for “scATAC-seq”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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4 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Inference of cell type-specific gene regulatory networks on cell lineages from single cell omic datasets

Abstract Cell type-specific gene expression patterns are outputs of transcriptional gene regulatory networks (GRNs) that connect transcription factors and signaling proteins to target genes. Single-cell technologies such as single cell RNA-sequencing (scRNA-seq) and single cell Assay for Transposase-Accessible Chromatin using sequencing (scATAC-seq), can examine cell-type specific gene regulation at unprecedented detail. However, current approaches to infer cell type-specific GRNs are limited in their ability to integrate scRNA-seq and scATAC-seq measurements and to model network dynamics on a cell lineage. To address this challenge, we have developed single-cell Multi-Task Network Inference (scMTNI), a multi-task learning framework to infer the GRN for each cell type on a lineage from scRNA-seq and scATAC-seq data. Using simulated and real datasets, we show that scMTNI is a broadly applicable framework for linear and branching lineages that accurately infers GRN dynamics and identifies key regulators of fate transitions for diverse processes such as cellular reprogramming and differentiation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Single-cell chromatin accessibility and cis -regulatory element analyses in plants using the scPlantReg platform

Understanding gene regulation is fundamental to plant improvement, but the lack of plant-specific single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) frameworks and cross-species databases has limited insights into cell-type-specific cellular regulation. Here we present ‘scPlantReg’, an integrated framework and database for plant scATAC-seq data. scPlantReg supports end-to-end analyses from raw data processing to biological interpretation and features ‘scATACtor’, a supervised machine-learning approach that outperforms existing tools for cell-type annotation. We applied scPlantReg to pearl millet to characterize cell-type-specific chromatin accessibility and identify validated activating and repressing accessible chromatin regions (ACRs), revealing WRKY transcription factors as potential regulators of xylem development. Furthermore, we reanalysed scATAC-seq datasets from 8 plant species, spanning 11 tissues and multiple developmental stages, enabling cross-species comparisons. Furthermore, these analyses uncovered conserved regulatory programmes, including AP2/EREBP-associated ACRs linked to cell wall development and cell-type-conserved TFs across grasses. Collectively, scPlantReg provides a general framework and resource for comparative regulatory analysis in plants.

Epigenomics↗
DOE OSTI2024

CrossMP: Enabling Cross-Modality Translation between Single-Cell RNA-Seq and Single-Cell ATAC-Seq through Web-Based Portal

In recent years, there has been a growing interest in profiling multiomic modalities within individual cells simultaneously. One such example is integrating combined single-cell RNA sequencing (scRNA-seq) data and single-cell transposase-accessible chromatin sequencing (scATAC-seq) data. Integrated analysis of diverse modalities has helped researchers make more accurate predictions and gain a more comprehensive understanding than with single-modality analysis. However, generating such multimodal data is technically challenging and expensive, leading to limited availability of single-cell co-assay data. Here, we propose a model for cross-modal prediction between the transcriptome and chromatin profiles in single cells. Our model is based on a deep neural network architecture that learns the latent representations from the source modality and then predicts the target modality. It demonstrates reliable performance in accurately translating between these modalities across multiple paired human scATAC-seq and scRNA-seq datasets. Additionally, we developed CrossMP, a web-based portal allowing researchers to upload their single-cell modality data through an interactive web interface and predict the other type of modality data, using high-performance computing resources plugged at the backend.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

sciCAN: single-cell chromatin accessibility and gene expression data integration via cycle-consistent adversarial network

The boom in single-cell technologies has brought a surge of high dimensional data that come from different sources and represent cellular systems from different views. With advances in these single-cell technologies, integrating single-cell data across modalities arises as a new computational challenge. Here, we present an adversarial approach, sciCAN, to integrate single-cell chromatin accessibility and gene expression data in an unsupervised manner. We benchmarked sciCAN with 5 existing methods in 5 scATAC-seq/scRNA-seq datasets, and we demonstrated that our method dealt with data integration with consistent performance across datasets and better balance of mutual transferring between modalities than the other 5 existing methods. We further applied sciCAN to 10X Multiome data and confirmed that the integrated representation preserves biological relationships within the hematopoietic hierarchy. Finally, we investigated CRISPR-perturbed single-cell K562 ATAC-seq and RNA-seq data to identify cells with related responses to different perturbations in these different modalities.

59 BASIC BIOLOGICAL SCIENCES↗