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Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark Kyun Kim, Sang-Won Lee, Dae-Yong Kim
The molecular mechanisms underlying the pathogenesis of diffuse-type gastric cancer (DGC) have not been adequately explored due to a scarcity of appropriate animal models. A recently developed tool well suited for this line of investigation is the Pdx-1-Cre;Cdh1F/+ ;Trp53F/F ;Smad4F/F (pChe PS) mouse model that spontaneously develops metastatic DGC showing nearly complete E-cadherin loss. Here, we performed a proteogenomic analysis to uncover the molecular changes induced by the concurrent targeting of E-cadherin, p53, and Smad4 loss...
March 12, 2018: Molecular Carcinogenesis
Li Wang, John A Wrobel, Ling Xie, DongXu Li, Giada Zurlo, Huali Shen, Pengyuan Yang, Zefeng Wang, Yibing Peng, Harsha P Gunawardena, Qing Zhang, Xian Chen
To discriminate the patient subpopulations with different clinical outcomes within each breast cancer (BC) subtype, we introduce a robust, clinical-practical, activity-based proteogenomic method that identifies, in their oncogenically active states, candidate biomarker genes bearing patient-specific transcriptomic/genomic alterations of prognostic value. First, we used the intronic splicing enhancer (ISE) probes to sort ISE-interacting trans-acting protein factors (trans-interactome) directly from a tumor tissue for subsequent mass spectrometry characterization...
February 27, 2018: Cell Chemical Biology
Yafeng Zhu, Lukas M Orre, Henrik J Johansson, Mikael Huss, Jorrit Boekel, Mattias Vesterlund, Alejandro Fernandez-Woodbridge, Rui M M Branca, Janne Lehtiö
Proteogenomics enable the discovery of novel peptides (from unannotated genomic protein-coding loci) and single amino acid variant peptides (derived from single-nucleotide polymorphisms and mutations). Increasing the reliability of these identifications is crucial to ensure their usefulness for genome annotation and potential application as neoantigens in cancer immunotherapy. We here present integrated proteogenomics analysis workflow (IPAW), which combines peptide discovery, curation, and validation. IPAW includes the SpectrumAI tool for automated inspection of MS/MS spectra, eliminating false identifications of single-residue substitution peptides...
March 2, 2018: Nature Communications
Seung-Eun Lee, JongKeon Song, Korbinian Bösl, André C Müller, Dijana Vitko, Keiryn L Bennett, Giulio Superti-Furga, Akhilesh Pandey, Richard K Kandasamy, Min-Sik Kim
Chromosome-centric Human Proteome Project aims at identifying and characterizing protein products encoded from all human protein-coding genes. As of early 2017, 19,837 protein-coding genes have been annotated in the neXtProt database including 2,691 missing proteins that have never been identified by mass spectrometry. Missing proteins may be low abundant in many cell types or expressed only in a few cell types in human body such as sperms in testis. In this study, we performed expression proteomics of two near haploid cell types such as HAP1 and KBM-7 to hunt for missing proteins...
February 23, 2018: Proteomics
G T Tsangaris, A K Anagnostopoulos
Pediatric brain tumors (PBTs) are the most common solid malignancies in childhood and continue to pose a serious burden to modern societies. Existing treatments impose debilitating effects on the developing child, highlighting the need for molecularly targeted treatments with reduced toxicity, and the necessity of markers that reliably assess efficacy of, and tumor response to targeted-therapies of PBTs. On this regard advances in technologies of protein identification and quantification, the large-scale, high-throughput investigation of the proteome, as well the newly-emerging field of "proteogenomics" aim to further our knowledge towards understanding the molecular pathophysiology of PBTs...
February 19, 2018: Journal of Proteomics
Neeloo Singh, Renu Goel, Ekta Jain
PURPOSE: Although in trypanosomatids, monoxeny (Leptomonas) is ancestral to dixeny (Leishmania), however clinical cases of visceral leishmanisis with Leptomonas co-infection are increasingly being reported from India. Using a proteogenomic approach, we carried out a detailed proteome analysis of these two kinetoplastid parasites viz. Leishmania and its sister Leptomonas, to catalog the key proteins associated with and therefore possibly responsible for phenotype changes in Leptomonas evolution and domestication as co-infection with Leishmania...
February 22, 2018: Proteomics. Clinical Applications
Nathan P Manes, Aleksandra Nita-Lazar
The enormous diversity of proteoforms produces tremendous complexity within cellular proteomes, facilitates intricate networks of molecular interactions, and constitutes a formidable analytical challenge for biomedical researchers. Currently, quantitative whole-proteome profiling often relies on non-targeted liquid chromatography-mass spectrometry (LC-MS), which samples proteoforms broadly, but can suffer from lower accuracy, sensitivity, and reproducibility compared with targeted LC-MS. Recent advances in bottom-up proteomics using targeted LC-MS have enabled previously unachievable identification and quantification of target proteins and posttranslational modifications within complex samples...
February 13, 2018: Journal of Proteomics
H B Mahesh, Pratigya Subba, Jayshree Advani, Meghana Deepak Shirke, Ramya Malarini Loganathan, S Chandana, S Shilpa, Oishi Chatterjee, Sneha M Pinto, Keshava Prasad, Malali Gowda
Santalum album (Indian sandalwood) is an important tropical evergreen tree, known for its fragrant heartwood-derived essential oil and its valuable carving wood. Here, we applied an integrated genomic, transcriptomic, and proteomic approach to assemble and annotate the Indian sandalwood genome. Our genome sequencing resulted in the establishment of a draft map of the smallest genome for any woody tree species to date (221 Mb). The genome annotation predicted 38,119 protein-coding genes and 27.42% repetitive DNA elements...
February 12, 2018: Plant Physiology
Manuel Tardaguila, Lorena de la Fuente, Cristina Marti, Cécile Pereira, Francisco Jose Pardo-Palacios, Hector Del Risco, Marc Ferrell, Maravillas Mellado, Marissa Macchietto, Kenneth Verheggen, Mariola Edelmann, Iakes Ezkurdia, Jesus Vazquez, Michael Tress, Ali Mortazavi, Lennart Martens, Susana Rodriguez-Navarro, Victoria Moreno-Manzano, Ana Conesa
High-throughput sequencing of full-length transcripts using long reads has paved the way for the discovery of thousands of novel transcripts, even in well-annotated mammalian species. The advances in sequencing technology have created a need for studies and tools that can characterize these novel variants. Here, we present SQANTI, an automated pipeline for the classification of long-read transcripts that can assess the quality of data and the preprocessing pipeline using 47 unique descriptors. We apply SQANTI to a neuronal mouse transcriptome using Pacific Biosciences (PacBio) long reads and illustrate how the tool is effective in characterizing and describing the composition of the full-length transcriptome...
February 9, 2018: Genome Research
Qiuming Yao, Zhou Li, Yang Song, S Joseph Wright, Xuan Guo, Susannah G Tringe, Malak M Tfaily, Ljiljana Paša-Tolić, Terry C Hazen, Benjamin L Turner, Melanie A Mayes, Chongle Pan
Phosphorus is a scarce nutrient in many tropical ecosystems, yet how soil microbial communities cope with growth-limiting phosphorus deficiency at the gene and protein levels remains unknown. Here, we report a metagenomic and metaproteomic comparison of microbial communities in phosphorus-deficient and phosphorus-rich soils in a 17-year fertilization experiment in a tropical forest. The large-scale proteogenomics analyses provided extensive coverage of many microbial functions and taxa in the complex soil communities...
January 22, 2018: Nature Ecology & Evolution
Giovanni Nassa, Giorgio Giurato, Giovanni Cimmino, Francesca Rizzo, Maria Ravo, Annamaria Salvati, Tuula A Nyman, Yafeng Zhu, Mattias Vesterlund, Janne Lehtiö, Paolo Golino, Alessandro Weisz, Roberta Tarallo
Platelet activation triggers thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies still fail to prevent thrombotic events in numerous patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how megakaryocyte-derived mRNAs are regulated in these anucleate cell fragments. Proteogenomics was applied here to investigate this phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor Activating Peptide...
January 11, 2018: Scientific Reports
Amanda L Creech, Ying S Ting, Scott P Goulding, John Fk Sauld, Dominik Barthelme, Michael S Rooney, Terri A Addona, Jennifer G Abelin
A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer-specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA-peptide binding data that may not completely capture the rules associated with endogenous processing and presentation...
January 3, 2018: Proteomics
Mark V Ivanov, Anna A Lobas, Lev I Levitsky, Sergei A Moshkovskii, Mikhail V Gorshkov
In a proteogenomic approach based on tandem mass spectrometry analysis of proteolytic peptide mixtures, customized exome or RNA-seq databases are employed for identifying protein sequence variants. However, the problem of variant peptide identification without personalized genomic data is important for a variety of applications. Following the recent proposal by Chick et al. (Nat. Biotechnol. 33, 743-749, 2015) on the feasibility of such variant peptide search, we evaluated two available approaches based on the previously suggested "open" search and the "brute-force" strategy...
January 3, 2018: Journal of the American Society for Mass Spectrometry
Charles T Yang, Dipankar Ghosh, Francis Beaudry
Following the internationalization of food production and manufacturing, a significant increase of food fraud was discovered, ranging from false label claims to the use of additives and fillers to increase profitability. The accidental or fraudulent mixing of animal products or by-products from different species is an important preoccupation for consumers with health or ethical concerns. Gelatin is widely used during food processing as well as in cosmetics, nutraceutics and medical formulations. It contains mainly type I, II and III collagen polypeptides...
December 26, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
Xiaohang Wu, Zhenzhen Liu, Xiayin Zhang, Dongni Wang, Erping Long, Jinghui Wang, Wangting Li, Weiyi Lai, Qianzhong Cao, Kunhua Hu, Weirong Chen, Haotian Lin, Yizhi Liu
BACKGROUND: The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization. METHODS: The total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ)...
December 19, 2017: BMC Ophthalmology
Ying-Chun Song, Gai-Xia Lu, Hong-Wei Zhang, Xiao-Ming Zhong, Xian-Ling Cong, Shao-Bo Xue, Rui Kong, Dan Li, Zheng-Yan Chang, Xiao-Feng Wang, Yun-Jie Zhang, Ran Sun, Li Chai, Ru-Ting Xie, Ming-Xiang Cai, Ming Sun, Wei-Qing Mao, Hui-Qiong Yang, Yun-Chao Shao, Su-Yun Fan, Ting-Miao Wu, Qing Xia, Zhong-Wei Lv, David A Fu, Yu-Shui Ma
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples...
November 14, 2017: Oncotarget
Nicolas Gallois, Béatrice Alpha-Bazin, Philippe Ortet, Mohamed Barakat, Laurie Piette, Justine Long, Catherine Berthomieu, Jean Armengaud, Virginie Chapon
Microbacterium oleivorans A9 is a uranium-tolerant actinobacteria isolated from the trench T22 located near the Chernobyl nuclear power plant. This site is contaminated with different radionuclides including uranium. To observe the molecular changes at the proteome level occurring in this strain upon uranyl exposure and understand molecular mechanisms explaining its uranium tolerance, we established its draft genome and used this raw information to perform an in-depth proteogenomics study. High-throughput proteomics were performed on cells exposed or not to 10μM uranyl nitrate sampled at three previously identified phases of uranyl tolerance...
December 6, 2017: Journal of Proteomics
Shiyong Ma, Ranjeeta Menon, Rebecca C Poulos, Jason W H Wong
Massively parallel DNA sequencing enables the detection of thousands of germline and somatic single nucleotide variants (SNVs) in cancer samples. The functional analysis of these mutations is often carried out through in silico predictions, with further downstream experimental validation rarely performed. Here, we examine the potential of using mass spectrometry-based proteomics data to further annotate the function of SNVs in cancer samples. RNA-seq and whole genome sequencing (WGS) data from Jurkat cells were used to construct a custom database of single amino acid variant (SAAV) containing peptides and identified over 1,000 such peptides in two Jurkat proteomics datasets...
November 10, 2017: Oncotarget
Arunima Srivastava, Chaitanya Kulkarni, Parag Mallick, Kun Huang, Raghu Machiraju
Utilization of single modality data to build predictive models in cancer results in a rather narrow view of most patient profiles. Some clinical facet s relate strongly to histology image features, e.g. tumor stages, whereas others are associated with genomic and proteomic variations (e.g. cancer subtypes and disease aggression biomarkers). We hypothesize that there are coherent "trans-omics" features that characterize varied clinical cohorts across multiple sources of data leading to more descriptive and robust disease characterization...
2018: Pacific Symposium on Biocomputing
Sardar Karash, Rohana Liyanage, Abdullah Qassab, Jackson O Lay, Young Min Kwon
Salmonella is an intracellular pathogen infecting a wide range of hosts and can survive in macrophages. An essential mechanism used by macrophages to eradicate Salmonella is production of reactive oxygen species. Here, we used proteogenomics to determine the candidate genes and proteins that have a role in resistance of S. Typhimurium to H2 O2 . For Tn-seq, a saturated Tn5 insertion library was grown in vitro under either 2.5 (H2 O2 L) or 3.5 mM H2 O2 (H2 O2 H). We identified two sets of overlapping genes required for resistance of S...
December 6, 2017: Scientific Reports
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