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 dat...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.展开更多
For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interac...For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interaction are based on cell level,there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection.Based on collected proteomic datasets from human lung,colon,kidney,liver,and heart,we constructed a virus-receptor network,a virus-interaction network,and a virus-perturbation network.In the tissue-specific networks associated with virus-host crosstalk,both common and different key hubs are revealed in diverse tissues.Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation.Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction.The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues,and the treatment of COVID-19 would be a complex task.展开更多
文摘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.
基金This work was supported by grants from the Ministry of Science and Technology(2017YFA0505500)the Strategic CAS Project(XDA12010000 and XDB3000000).
文摘For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interaction are based on cell level,there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection.Based on collected proteomic datasets from human lung,colon,kidney,liver,and heart,we constructed a virus-receptor network,a virus-interaction network,and a virus-perturbation network.In the tissue-specific networks associated with virus-host crosstalk,both common and different key hubs are revealed in diverse tissues.Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation.Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction.The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues,and the treatment of COVID-19 would be a complex task.
