RT Journal Article
SR Electronic
T1 Revealing missing isoforms encoded in the human genome by integrating genomic, transcriptomic and proteomic data
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 012112
DO 10.1101/012112
A1 Zhiqiang Hu
A1 Hamish S. Scott
A1 Guangrong Qin
A1 Guangyong Zheng
A1 Xixia Chu
A1 Lu Xie
A1 David L. Adelson
A1 Bergithe E. Oftedal
A1 Parvalthy Venugopal
A1 Milena Babic
A1 Christopher N. Hahn
A1 Bing Zhang
A1 Xiaojing Wang
A1 Nan Li
A1 Chaochun Wei
YR 2014
UL http://biorxiv.org/content/early/2014/12/04/012112.abstract
AB 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 and is much larger than the number of human genes.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.