HMPA：从发现到功能洞察的非典型肽组前沿框架

HMPA: a pioneering framework for the noncanonical peptidome from discovery to functional insights

BRIEFINGS IN BIOINFORMATICS

影响因子:7.7

分区:生物学2区 / 数学与计算生物学1区生化研究方法2区

发表日期:2024 Sep 23

作者: Xinwan Su, Chengyu Shi, Fangzhou Liu, Manman Tan, Ying Wang, Linyu Zhu, Yu Chen, Meng Yu, Xinyi Wang, Jian Liu, Yang Liu, Weiqiang Lin, Zhaoyuan Fang, Qiang Sun, Tianhua Zhou, Aifu Lin

DOI: 10.1093/bib/bbae510

摘要

肽组学的进展揭示了大量具有编码潜能的小的开放阅读框（ORFs），其中一些微肽与人类癌症密切相关。然而，从序列到结构再到功能的系统性分析和整合仍处于初步阶段。作为解决方案，我们建立了一个工作流程，用于利用公开大规模队列数据集收集和分析与癌症相关的微肽的蛋白质组学数据、转录组数据及临床结局。我们通过重新分析3753个样本在8种癌症中的蛋白质组数据，最初鉴定出19586个新颖微肽。进一步结合这些微肽的定量分析和临床数据，筛选出在癌症中异常表达的3065个微肽，其中370个与预后密切相关。此外，我们采用深度学习框架，构建了微肽-蛋白相互作用网络，揭示微肽作为生物活性分子参与多种生物过程。综上所述，我们的图谱为微肽的高通量预测和功能探索提供了基准，为其在癌症中的生物机制提供了新见解。HMPA免费提供，网址为http://hmpa.zju.edu.cn。

Abstract

Advancements in peptidomics have revealed numerous small open reading frames with coding potential and revealed that some of these micropeptides are closely related to human cancer. However, the systematic analysis and integration from sequence to structure and function remains largely undeveloped. Here, as a solution, we built a workflow for the collection and analysis of proteomic data, transcriptomic data, and clinical outcomes for cancer-associated micropeptides using publicly available datasets from large cohorts. We initially identified 19 586 novel micropeptides by reanalyzing proteomic profile data from 3753 samples across 8 cancer types. Further quantitative analysis of these micropeptides, along with associated clinical data, identified 3065 that were dysregulated in cancer, with 370 of them showing a strong association with prognosis. Moreover, we employed a deep learning framework to construct a micropeptide-protein interaction network for further bioinformatics analysis, revealing that micropeptides are involved in multiple biological processes as bioactive molecules. Taken together, our atlas provides a benchmark for high-throughput prediction and functional exploration of micropeptides, providing new insights into their biological mechanisms in cancer. The HMPA is freely available at http://hmpa.zju.edu.cn.