ATACompass enables cross-species cell identity mapping for scATAC-seq without gene annotations.

Area of Science:

• Genomics
• Computational Biology
• Epigenetics

Background:

• Single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) is crucial for understanding transcriptional regulation.
• Cell identity annotation in scATAC-seq faces challenges like data sparsity and limited gene annotations, especially in non-model organisms.

Purpose of the Study:

• To develop a novel sequence-based framework, ATACompass, for accurate cell identity annotation in scATAC-seq data.
• To overcome limitations in annotating non-model organisms and enable cross-species cell annotation.

Main Methods:

• ATACompass encodes chromatin accessibility peak sequences using the HyenaDNA foundation model and large language models.
• Controlled sequence mutations were employed for data augmentation.
• The framework was evaluated on intra-species and cross-species annotation tasks.

Main Results:

• ATACompass demonstrated competitive or superior performance compared to state-of-the-art methods in intra-species tasks.
• The framework successfully enabled zero-shot cross-species cell annotation by utilizing conserved sequences.
• Integrating datasets across evolutionary lineages improved predictive accuracy for comprehensive annotation.

Conclusions:

• ATACompass offers a gene annotation-independent approach for cell type and regulatory landscape studies.
• This framework significantly advances cell annotation capabilities, particularly for non-model organisms.