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

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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
JournalJournal of Molecular Cell Biology
Issue number5
Publication statusPublished - 2014
Externally publishedYes


  • De novo
  • Human brain tissues
  • Proteomics
  • Single amino-acid variants (SAVs)


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