@article{5b1a7f92f2ee417f98a72a4783fe5c04,
title = "Revealing Missing Human Protein Isoforms Based on Ab Initio Prediction, RNA-seq and Proteomics",
abstract = "Biological and biomedical research relies on comprehensive understanding of protein-coding transcripts. However, the total number of human proteins is still unknown due to the prevalence of alternative splicing. In this paper, we detected 31,566 novel transcripts with coding potential by filtering our ab initio predictions with 50 RNA-seq datasets from diverse tissues/cell lines. PCR followed by MiSeq sequencing showed that at least 84.1% of these predicted novel splice sites could be validated. In contrast to known transcripts, the expression of these novel transcripts were highly tissue-specific. Based on these novel transcripts, at least 36 novel proteins were detected from shotgun proteomics data of 41 breast samples. We also showed L1 retrotransposons have a more significant impact on the origin of new transcripts/genes than previously thought. Furthermore, we found that alternative splicing is extraordinarily widespread for genes involved in specific biological functions like protein binding, nucleoside binding, neuron projection, membrane organization and cell adhesion. In the end, the total number of human transcripts with protein-coding potential was estimated to be at least 204,950.",
author = "Zhiqiang Hu and Scott, {Hamish S.} and Guangrong Qin and Guangyong Zheng and Xixia Chu and Lu Xie and Adelson, {David L.} and Oftedal, {Bergithe E.} and Parvathy Venugopal and Milena Babic and Hahn, {Christopher N.} and Bing Zhang and Xiaojing Wang and Nan Li and Chaochun Wei",
note = "Funding Information: We thank Dr. Hagen Tilgner and Dr. Michael Snyder for providing transcript data with PacBio sequencing support. We thank Dr. Guohui Ding from Chinese Academy of Science and Dr. Yuanyuan Li from Shanghai Center for Bioinformation Technology for their helpful discussion and insightful comments. We thank the High Performance Computing Center (HPCC) at Shanghai Jiao Tong University for the computation. Thanks to the staff of the ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide. This work was supported by grants from the National Natural Science Foundation of China (61272250, 61472246), the National Basic Research Program of China (2013CB956103, 2010CB912702), and the National High-Tech R&D Program (863) (2012AA101601 and 2014AA021502). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",
year = "2015",
month = jul,
day = "9",
doi = "10.1038/srep10940",
language = "English (US)",
volume = "5",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}