Details

Autor(en) / Beteiligte

• Su, Zhi-Duan
• Sheng, Quan-Hu
• Li, Qing-Run
• Chi, Hao
• Jiang, Xi
• Yan, Zheng
• Fu, Ning
• He, Si-Min
• Khaitovich, Philipp
• Wu, Jia-Rui
• Zeng, Rong

Titel

De novo identification and quantification of single amino-acid variants in human brain

Ist Teil von

• Journal of molecular cell biology, 2014-10, Vol.6 (5), p.421-433

Ort / Verlag

United States

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• The detection of single amino-acid variants (SAVs) usually depends on single-nucleotide polymorphisms (SNPs) database. Here, we describe a novel method that discovers SAVs at proteome level independent of SNPs data. Using mass spectrometry-based de novo sequencing algorithm, peptide-candidates are identified and compared with theoretical protein database to generate SAVs under pairing strategy, which is followed by database re-searching to control false discovery rate. In human brain tissues, we can confidently identify known and novel protein variants with diverse origins. Combined with DNA/RNA sequencing, we verify SAVs derived from DNA mutations, RNA alternative splicing, and unknown post-transcriptional mechanisms. Furthermore, quantitative analysis in human brain tissues reveals several tissue-specific differential expressions of SAVs. This approach provides a novel access to high-throughput detection of protein variants, which may offer the potential for clinical biomarker discovery and mechanistic research.