ChromBERT-tools: A versatile toolkit for context-specific embedding of transcription regulators across different cell types

Abstract Motivation Representations that capture the genome-wide context of transcription regulators are critical for establishing a shared backbone for flexible transcription modeling and in silico regulatory analysis. Yet, current embeddings predominantly rely on limited modalities, such as gene co-expression or static protein features, offering an incomplete perspective that ignores context-dependent transcription regulator activities across the genome. The lack of transcription regulation-informed embeddings, paired with the absence of a user-friendly and lightweight toolkit for their generation, adaption to different cell types and interpretation, impedes the capture of the regulatory logic that underpin cellular states and functions. Results To address this need, we present ChromBERT-tools, a lightweight toolkit designed to operationalize regulation-informed embeddings derived from a foundation model pre-trained on the comprehensive landscapes of human and mouse transcription regulators. ChromBERT-tools provides user-friendly command-line interfaces (CLIs) and Python APIs to achieve two primary goals: (i) generating cell-type-agnostic embeddings that capture the semantic representations of individual regulators and their combinatorial interactions, serving as biological priors of transcription regulator modality to enhance transcription regulation modeling and rule interpretation; and (ii) generating cell-type-specific embeddings via fine-tuned model variants, which support in silico inference of regulatory roles of transcription regulators in cell types with scarce experimental data. The toolkit streamlines end-to-end workflows for embedding generation, adaption to different cell types and interpretation towards biological inferences such as regulator-regulator interaction across the genome and key regulators determining cell identity or cell state transition. Availability and implementation ChromBERT-tools is freely available at https://github.com/TongjiZhanglab/ChromBERT-tools , with documentation at https://chrombert-tools.readthedocs.io/en/latest/ .