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An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

An Ultrahigh-throughput Microfluidic Platform for Single-cell Genome Sequencing

Published on: May 23, 2018

scooby: Modeling multi-modal genomic profiles from DNA sequence at single-cell resolution.

Johannes C Hingerl^1,2, Laura D Martens^1,3, Alexander Karollus^1,2

¹School of Computation, Information and Technology, Technical University of Munich, Munich, Germany.

Biorxiv : the Preprint Server for Biology

|September 30, 2024

Summary

Introducing scooby, a novel framework for single-cell genomics. It models gene expression and chromatin accessibility from DNA sequence, revealing cell-specific regulatory mechanisms and variant effects.

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A Combinatorial Single-cell Approach to Characterize the Molecular and Immunophenotypic Heterogeneity of Human Stem and Progenitor Populations

Published on: October 25, 2018

Area of Science:

Genomics
Molecular Biology
Computational Biology

Background:

Understanding gene regulation in individual cells is crucial but challenging.
Current models struggle with cellular heterogeneity from single-cell multi-modal data.
Existing methods fail to capture dynamic gene expression processes at single-cell resolution.

Purpose of the Study:

To introduce scooby, the first framework for modeling single-cell RNA-seq (scRNA-seq) and single-cell ATAC-seq (scATAC-seq) data.
To capture sequence determinants of gene regulation at single-cell resolution.
To enable accurate variant effect prediction in single cells.

Main Methods:

Leveraging the Borzoi foundation model for multi-omics profile prediction.
Developing a cell-specific decoder conditioned on single-cell embeddings.
Fine-tuning sequence embeddings for enhanced generalization capability.

Main Results:

scooby successfully models scRNA-seq coverage and scATAC-seq insertion profiles.
It recapitulates cell-specific gene expression and identifies regulatory elements.
Accurate prediction of variant effects, breaking down bulk eQTLs into single-cell impacts.

Conclusions:

scooby provides a powerful tool for dissecting gene regulation at single-cell resolution.
It advances the understanding of chromatin accessibility and gene expression dynamics.
The framework facilitates the study of genetic variant impacts on cellular processes.