Life-Code: Central Dogma Modeling with Multi-Omics Sequence Unification

Fuente: arXiv
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Auteurs principaux: Liu, Zicheng, Li, Siyuan, Chen, Zhiyuan, Yu, Chang, Yang, Qirong, Guo, Yucheng, Yang, Yujie, Zhang, Xiaoming, Li, Stan Z.
Format: Preprint
Publié: 2025
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author Liu, Zicheng
Li, Siyuan
Chen, Zhiyuan
Yu, Chang
Yang, Qirong
Guo, Yucheng
Yang, Yujie
Zhang, Xiaoming
Li, Stan Z.
author_facet Liu, Zicheng
Li, Siyuan
Chen, Zhiyuan
Yu, Chang
Yang, Qirong
Guo, Yucheng
Yang, Yujie
Zhang, Xiaoming
Li, Stan Z.
contents The interactions between DNA, RNA, and proteins are fundamental to biological processes, as illustrated by the central dogma of molecular biology. Although modern biological pre-trained models have achieved great success in analyzing these macromolecules individually, their interconnected nature remains underexplored. This paper follows the guidance of the central dogma to redesign both the data and model pipeline and offers a comprehensive framework, Life-Code, that spans different biological functions. As for data flow, we propose a unified pipeline to integrate multi-omics data by reverse-transcribing RNA and reverse-translating amino acids into nucleotide-based sequences. As for the model, we design a codon tokenizer and a hybrid long-sequence architecture to encode the interactions between coding and non-coding regions through masked modeling pre-training. To model the translation and folding process with coding sequences, Life-Code learns protein structures of the corresponding amino acids by knowledge distillation from off-the-shelf protein language models. Such designs enable Life-Code to capture complex interactions within genetic sequences, providing a more comprehensive understanding of multi-omics with the central dogma. Extensive experiments show that Life-Code achieves state-of-the-art results on various tasks across three omics, highlighting its potential for advancing multi-omics analysis and interpretation.
format Preprint
id arxiv_https___arxiv_org_abs_2502_07299
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Life-Code: Central Dogma Modeling with Multi-Omics Sequence Unification
Liu, Zicheng
Li, Siyuan
Chen, Zhiyuan
Yu, Chang
Yang, Qirong
Guo, Yucheng
Yang, Yujie
Zhang, Xiaoming
Li, Stan Z.
Machine Learning
Artificial Intelligence
Computation and Language
Genomics
The interactions between DNA, RNA, and proteins are fundamental to biological processes, as illustrated by the central dogma of molecular biology. Although modern biological pre-trained models have achieved great success in analyzing these macromolecules individually, their interconnected nature remains underexplored. This paper follows the guidance of the central dogma to redesign both the data and model pipeline and offers a comprehensive framework, Life-Code, that spans different biological functions. As for data flow, we propose a unified pipeline to integrate multi-omics data by reverse-transcribing RNA and reverse-translating amino acids into nucleotide-based sequences. As for the model, we design a codon tokenizer and a hybrid long-sequence architecture to encode the interactions between coding and non-coding regions through masked modeling pre-training. To model the translation and folding process with coding sequences, Life-Code learns protein structures of the corresponding amino acids by knowledge distillation from off-the-shelf protein language models. Such designs enable Life-Code to capture complex interactions within genetic sequences, providing a more comprehensive understanding of multi-omics with the central dogma. Extensive experiments show that Life-Code achieves state-of-the-art results on various tasks across three omics, highlighting its potential for advancing multi-omics analysis and interpretation.
title Life-Code: Central Dogma Modeling with Multi-Omics Sequence Unification
topic Machine Learning
Artificial Intelligence
Computation and Language
Genomics
url https://arxiv.org/abs/2502.07299