PMID- 25265570
OWN - NLM
STAT- MEDLINE
DCOM- 20150819
LR  - 20211021
IS  - 1615-9861 (Electronic)
IS  - 1615-9853 (Print)
IS  - 1615-9853 (Linking)
VI  - 14
IP  - 23-24
DP  - 2014 Dec
TI  - Revisiting the identification of canonical splice isoforms through integration of 
      functional genomics and proteomics evidence.
PG  - 2709-18
LID - 10.1002/pmic.201400170 [doi]
AB  - Canonical isoforms in different databases have been defined as the most 
      prevalent, most conserved, most expressed, longest, or the one with the clearest 
      description of domains or posttranslational modifications. In this article, we 
      revisit these definitions of canonical isoforms based on functional genomics and 
      proteomics evidence, focusing on mouse data. We report a novel functional 
      relationship network-based approach for identifying the highest connected 
      isoforms (HCIs). We show that 46% of these HCIs are not the longest transcripts. 
      In addition, this approach revealed many genes that have more than one highly 
      connected isoforms. Averaged across 175 RNA-seq datasets covering diverse tissues 
      and conditions, 65% of the HCIs show higher expression levels than nonhighest 
      connected isoforms at the transcript level. At the protein level, these HCIs 
      highly overlap with the expressed splice variants, based on proteomic data from 
      eight different normal tissues. These results suggest that a more confident 
      definition of canonical isoforms can be made through integration of multiple 
      lines of evidence, including HCIs defined by biological processes and pathways, 
      expression prevalence at the transcript level, and relative or absolute abundance 
      at the protein level. This integrative proteogenomics approach can successfully 
      identify principal isoforms that are responsible for the canonical functions of 
      genes.
CI  - (c) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Li, Hong-Dong
AU  - Li HD
AD  - Department of Computational Medicine and Bioinformatics, University of Michigan, 
      Ann Arbor, MI, USA.
FAU - Menon, Rajasree
AU  - Menon R
FAU - Omenn, Gilbert S
AU  - Omenn GS
FAU - Guan, Yuanfang
AU  - Guan Y
LA  - eng
GR  - U54ES017885/ES/NIEHS NIH HHS/United States
GR  - R21 NS082212/NS/NINDS NIH HHS/United States
GR  - R35 GM133346/GM/NIGMS NIH HHS/United States
GR  - RM08029/RM/RMOD NIH HHS/United States
GR  - P30 ES017885/ES/NIEHS NIH HHS/United States
GR  - 1R21NS082212-01/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141117
PL  - Germany
TA  - Proteomics
JT  - Proteomics
JID - 101092707
RN  - 0 (Protein Isoforms)
SB  - IM
MH  - Alternative Splicing/*genetics
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Protein Isoforms/*metabolism
MH  - Proteomics/*methods
PMC - PMC4372202
MID - NIHMS647585
OTO - NOTNLM
OT  - Alternative splicing
OT  - Canonical isoforms
OT  - Highest connected isoforms
OT  - Integrative proteogenomics
OT  - Major transcripts
COIS- Conflict of interest statement The authors have declared no conflict of interest.
EDAT- 2014/09/30 06:00
MHDA- 2015/08/20 06:00
PMCR- 2015/12/01
CRDT- 2014/09/30 06:00
PHST- 2014/04/28 00:00 [received]
PHST- 2014/08/11 00:00 [revised]
PHST- 2014/09/23 00:00 [accepted]
PHST- 2014/09/30 06:00 [entrez]
PHST- 2014/09/30 06:00 [pubmed]
PHST- 2015/08/20 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1002/pmic.201400170 [doi]
PST - ppublish
SO  - Proteomics. 2014 Dec;14(23-24):2709-18. doi: 10.1002/pmic.201400170. Epub 2014 
      Nov 17.