A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway

TNF-related weak inducer of apoptosis (TWEAK) is a new member of the TNF superfamily. It signals through TNFRSF12A, commonly known as Fn14. The TWEAK-Fn14 interaction regulates cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, tissue remodeling and inflammation. Although TWEAK has been reported to be associated with autoimmune diseases, cancers, stroke, and kidney-related disorders, the downstream molecular events of TWEAK-Fn14 signaling are yet not available in any signaling pathway repository. In this paper, we manually compiled from the literature, in particular those reported in human systems, the downstream reactions stimulated by TWEAK-Fn14 interactions. Our manual amassment of the TWEAK-Fn14 pathway has resulted in cataloging of 46 proteins involved in various biochemical reactions and TWEAK-Fn14 induced expression of 28 genes. We have enabled the availability of data in various standard exchange formats from NetPath, a repository for signaling pathways. We believe that this composite molecular interaction pathway will enable identification of new signaling components in TWEAK signaling pathway. This in turn may lead to the identification of potential therapeutic targets in TWEAK-associated disorders

Brain proteomics of anopheles gambiae

Anopheles gambiae has a well-adapted system for host localization, feeding, and mating behavior, which are all governed by neuronal processes in the brain. However, there are no published reports characterizing the brain proteome to elucidate neuronal signaling mechanisms in the vector. To this end, a large-scale mapping of the brain proteome of An. gambiae was carried out using high resolution tandem mass spectrometry, revealing a repertoire of \u3e1800 proteins, of which 15% could not be assigned any function. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including metabolism, transport, protein synthesis, and olfaction. This study also led to the identification of 10 GPCR classes of proteins, which could govern sensory pathways in mosquitoes. Proteins involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission were predominantly expressed in the brain. Proteogenomic analysis expanded our findings with the identification of 15 novel genes and 71 cases of gene refinements, a subset of which were validated by RT-PCR and sequencing. Overall, our study offers valuable insights into the brain physiology of the vector that could possibly open avenues for intervention strategies for malaria in the future. © Copyright 2014, Mary Ann Liebert, Inc. 2014

Brain Proteomics of Anopheles gambiae

Anopheles gambiae has a well-adapted system for host localization, feeding, and mating behavior, which are all governed by neuronal processes in the brain. However, there are no published reports characterizing the brain proteome to elucidate neuronal signaling mechanisms in the vector. To this end, a large-scale mapping of the brain proteome of An. gambiae was carried out using high resolution tandem mass spectrometry, revealing a repertoire of >1800 proteins, of which 15% could not be assigned any function. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including metabolism, transport, protein synthesis, and olfaction. This study also led to the identification of 10 GPCR classes of proteins, which could govern sensory pathways in mosquitoes. Proteins involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission were predominantly expressed in the brain. Proteogenomic analysis expanded our findings with the identification of 15 novel genes and 71 cases of gene refinements, a subset of which were validated by RT-PCR and sequencing. Overall, our study offers valuable insights into the brain physiology of the vector that could possibly open avenues for intervention strategies for malaria in the future

Proteogenomic Analysis of <i>Candida glabrata</i> using High Resolution Mass Spectrometry

<i>Candida glabrata</i> is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of <i>C. glabrata</i> using high resolution Fourier transform mass spectrometry with MS resolution of 60000 and MS/MS resolution of 7500. On the basis of 32453 unique peptides identified from 118815 peptide–spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the <i>C. glabrata</i> genome. Further, searching the tandem mass spectra against a six frame translated genome database of <i>C. glabrata</i> resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts

Proteogenomic Analysis of <i>Candida glabrata</i> using High Resolution Mass Spectrometry

<i>Candida glabrata</i> is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of <i>C. glabrata</i> using high resolution Fourier transform mass spectrometry with MS resolution of 60000 and MS/MS resolution of 7500. On the basis of 32453 unique peptides identified from 118815 peptide–spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the <i>C. glabrata</i> genome. Further, searching the tandem mass spectra against a six frame translated genome database of <i>C. glabrata</i> resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts

Proteogenomic Analysis of <i>Candida glabrata</i> using High Resolution Mass Spectrometry

<i>Candida glabrata</i> is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of <i>C. glabrata</i> using high resolution Fourier transform mass spectrometry with MS resolution of 60000 and MS/MS resolution of 7500. On the basis of 32453 unique peptides identified from 118815 peptide–spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the <i>C. glabrata</i> genome. Further, searching the tandem mass spectra against a six frame translated genome database of <i>C. glabrata</i> resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts

Proteogenomic Analysis of <i>Candida glabrata</i> using High Resolution Mass Spectrometry

<i>Candida glabrata</i> is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of <i>C. glabrata</i> using high resolution Fourier transform mass spectrometry with MS resolution of 60000 and MS/MS resolution of 7500. On the basis of 32453 unique peptides identified from 118815 peptide–spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the <i>C. glabrata</i> genome. Further, searching the tandem mass spectra against a six frame translated genome database of <i>C. glabrata</i> resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts

Proteogenomic Analysis of <i>Candida glabrata</i> using High Resolution Mass Spectrometry

<i>Candida glabrata</i> is a common opportunistic human pathogen leading to significant mortality in immunosuppressed and immunodeficient individuals. We carried out proteomic analysis of <i>C. glabrata</i> using high resolution Fourier transform mass spectrometry with MS resolution of 60000 and MS/MS resolution of 7500. On the basis of 32453 unique peptides identified from 118815 peptide–spectrum matches, we validated 4421 of the 5283 predicted protein-coding genes (83%) in the <i>C. glabrata</i> genome. Further, searching the tandem mass spectra against a six frame translated genome database of <i>C. glabrata</i> resulted in identification of 11 novel protein coding genes and correction of gene boundaries for 14 predicted gene models. A subset of novel protein-coding genes and corrected gene models were validated at the transcript level by RT-PCR and sequencing. Our study illustrates how proteogenomic analysis enabled by high resolution mass spectrometry can enrich genome annotation and should be an integral part of ongoing genome sequencing and annotation efforts