University of Michigan Center for Computational Medicine and Bioinformatics and Michigan Proteomics Alliance for Cancer Research, Ann Arbor, MI 48109-2218, USA.
Dis Markers. 2010;28(4):241-51. doi: 10.3233/DMA-2010-0702.
Alternative splicing plays an important role in protein diversity without increasing genome size. Earlier thought to be uncommon, splicing appears to affect the majority of genes. Alternative splice variants have been detected at the mRNA level in many diseases. We have designed and demonstrated a discovery pipeline for alternative splice variant (ASV) proteins from tandem MS/MS datasets. We created a modified ECgene database with entries from exhaustive three-frame translation of Ensembl transcripts and gene models from ECgene, with periodic updates. The human database has 14 million entries; the mouse database, 10 million entries. We match MS/MS findings against these potential translation products to identify and quantify known and novel ASVs. In this review, we summarize findings and systems biology implications of biomarker candidates from a mouse model of human pancreatic ductal adenocarcinoma [28] and a mouse model of human Her2/neu-induced breast cancer [27]. The same approach is being applied to human tumors, plasma, and cell line studies of other cancers.
选择性剪接在不增加基因组大小的情况下对蛋白质多样性起着重要作用。早期认为这种剪接方式并不常见，但实际上它似乎影响了大多数基因。在许多疾病中，在 mRNA 水平上已经检测到了选择性剪接变体。我们设计并展示了一种从串联 MS/MS 数据集发现选择性剪接变体 (ASV) 蛋白的发现管道。我们创建了一个经过修改的 ECgene 数据库，其中包含来自 Ensembl 转录本和 ECgene 基因模型的全面三框架翻译的条目，并定期进行更新。人类数据库有 1400 万条条目；老鼠数据库有 1000 万条条目。我们将 MS/MS 结果与这些潜在的翻译产物进行匹配，以识别和定量已知和新的 ASV。在这篇综述中，我们总结了人类胰腺导管腺癌 [28] 和人类 Her2/neu 诱导的乳腺癌 [27] 小鼠模型中的生物标志物候选物的发现和系统生物学意义。同样的方法也应用于人类肿瘤、血浆和其他癌症的细胞系研究。
