In recent years, the emphasis of scientific inquiry has shifted from whole-genome analyses to an understanding of cellular responses specific to tissue, developmental stage or environmental conditions. One of the central mechanisms underlying the diversity and adaptability of the contextual responses is alternative splicing (AS). It enables a single gene to encode multiple isoforms with distinct biological functions. However, to date, the functions of the vast majority of differentially spliced protein isoforms are not known. Integration of genomic, proteomic, functional, phenotypic and contextual information is essential for supporting isoform-based modeling and analysis. Such integrative proteogenomics approaches promise to provide insights into the functions of the alternatively spliced protein isoforms and provide high-confidence hypotheses to be validated experimentally. This manuscript provides a survey of the public databases supporting isoform-based biology. It also presents an overview of the potential global impact of AS on the human canonical gene functions, molecular interactions and cellular pathways.

中文翻译：

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使用可用的注释来源探索替代剪接对人类蛋白质同工型的功能影响。

近年来，科学探究的重点已从全基因组分析转向对组织，发育阶段或环境条件特异的细胞反应的理解。上下文响应的多样性和适应性所基于的中心机制之一是替代剪接（AS）。它使单个基因能够编码具有不同生物学功能的多种同工型。然而，迄今为止，绝大多数差异剪接蛋白同工型的功能尚不清楚。基因组，蛋白质组学，功能，表型和背景信息的集成对于支持基于异构体的建模和分析至关重要。这种整合的蛋白质组学方法有望提供对选择性剪接的蛋白质同工型的功能的见解，并提供可以通过实验验证的高可信度假设。该手稿对支持基于异构体的生物学的公共数据库进行了调查。它还概述了AS对人类规范基因功能，分子相互作用和细胞途径的潜在全球影响。