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https://www.readbyqxmd.com/read/28317871/insights-into-molecular-therapy-of-glioma-current-challenges-and-next-generation-blueprint
#1
REVIEW
Y Rajesh, Ipsita Pal, Payel Banik, Sandipan Chakraborty, Sachin A Borkar, Goutam Dey, Ahona Mukherjee, Mahitosh Mandal
Glioma accounts for the majority of human brain tumors. With prevailing treatment regimens, the patients have poor survival rates. In spite of current development in mainstream glioma therapy, a cure for glioma appears to be out of reach. The infiltrative nature of glioma and acquired resistance substancially restrict the therapeutic options. Better elucidation of the complicated pathobiology of glioma and proteogenomic characterization might eventually open novel avenues for the design of more sophisticated and effective combination regimens...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317375/comparison-of-false-discovery-rate-control-strategies-for-variant-peptide-identifications-in-shotgun-proteogenomics
#2
Mark V Ivanov, Anna A Lobas, Dmitry S Karpov, Sergei A Moshkovskii, Mikhail V Gorshkov
Proteogenomic studies aiming at identification of variant peptides using customized database searches of mass spectrometry data are facing a dilemma of selecting the most efficient database search strategy: a choice has to be made between using combined or sequential searches against reference (wild-type) and mutant protein databases, or directly against the mutant database without the wild-type one. Here, we called these approaches "all-together", "one-by-one" and "direct", respectively. In this note we would like to share the results of comparison of these search strategies obtained for large data sets of publicly available proteogenomic data...
March 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28286965/harnessing-the-power-of-proteomics-for-identification-of-oncogenic-druggable-signalling-pathways-in-cancer
#3
Heather C Murray, Matthew D Dun, Nicole M Verrills
Genomic and transcriptomic profiling of tumours has revolutionised our understanding of cancer. However, the majority of tumours possess multiple mutations, and determining which oncogene, or even which pathway, to target is difficult. Proteomics is emerging as a powerful approach to identify the functionally important pathways driving these cancers, and how they can be targeted therapeutically. Areas Covered: The authors provide a technical overview of mass spectrometry based approaches for proteomic profiling, and review the current and emerging strategies available for the identification of dysregulated networks, pathways, and drug targets in cancer cells, with a key focus on the ability to profile cancer kinomes...
March 13, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28276747/proteogenomic-studies-on-cancer-drug-resistance-towards-biomarker-discovery-and-target-identification
#4
Shuyue Fu, Xiang Liu, Maochao Luo, Ke Xie, Edouard C Nice, Haiyuan Zhang, Canhua Huang
Chemoresistance is a major obstacle for current cancer treatment. Proteogenomics is a powerful multi-omics research field that uses customized protein sequence databases generated by genomic and transcriptomic information to identify novel genes (e.g. noncoding, mutation and fusion genes) from mass spectrometry-based proteomic data. By identifying aberrations that are differentially expressed between tumor and normal pairs, this approach can also be applied to validate protein variants in cancer, which may reveal the response to drug treatment...
March 6, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28271730/recent-mass-spectrometry-based-proteomics-for-biomarker-discovery-in-lung-cancer-copd-and-asthma
#5
Kiyonaga Fujii, Haruhiko Nakamura, Toshihide Nishimura
Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches...
March 17, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28187513/collaboration-to-accelerate-proteogenomics-cancer-care-the-department-of-veterans-affairs-department-of-defense-and-the-national-cancer-institute-s-applied-proteogenomics-organizational-and-learning-apollo-network
#6
L D Fiore, H Rodriguez, C D Shriver
The ability to interrogate cancer at the proteogenomic level has the potential to transform oncology care from trial-and-error treatment strategies based on the anatomy and genomic profiling of tumors to one that is precisely based on the tumor's molecular profile. The next step in the evolution of precision oncology is developing proteogenomic approaches that make no exclusive assumptions a priori as to the molecular level of the patient's disease. The DoD, VA, and NCI responded to the Cancer Moonshot initiative by linking each agency's unique capabilities in clinical and basic science, computing, and high-throughput sequencing...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28187409/pgminer-reloaded-fully-automated-proteogenomic-annotation-tool-linking-genomes-to-proteomes
#7
Canan Has, Sergey A Lashin, Alexey V Kochetov, Jens Allmer
Improvements in genome sequencing technology increased the availability of full genomes and transcriptomes of many organisms. However, the major benefit of massive parallel sequencing is to better understand the organization and function of genes which then lead to understanding of phenotypes. In order to interpret genomic data with automated gene annotation studies, several tools are currently available. Even though the accuracy of computational gene annotation is increasing, a combination of multiple lines of experimental evidences should be gathered...
December 18, 2016: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28184370/metaproteomics-as-a-complementary-approach-to-gut-microbiota-in-health-and-disease
#8
REVIEW
Bernardo A Petriz, Octávio L Franco
Classic studies on phylotype profiling are limited to the identification of microbial constituents, where information is lacking about the molecular interaction of these bacterial communities with the host genome and the possible outcomes in host biology. A range of OMICs approaches have provided great progress linking the microbiota to health and disease. However, the investigation of this context through proteomic mass spectrometry-based tools is still being improved. Therefore, metaproteomics or community proteogenomics has emerged as a complementary approach to metagenomic data, as a field in proteomics aiming to perform large-scale characterization of proteins from environmental microbiota, such as the human gut...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28157690/variant-peptide-detection-utilizing-mass-spectrometry-laying-the-foundations-for-proteogenomic-identification-and-validation
#9
Lampros Dimitrakopoulos, Ioannis Prassas, Els M J J Berns, John A Foekens, Eleftherios P Diamandis, George S Charames
BACKGROUND: Proteogenomics is an emerging field at the intersection of genomics and proteomics. Many variant peptides corresponding to single nucleotide variations (SNVs) are associated with specific diseases. The aim of this study was to demonstrate the feasibility of proteogenomic-based variant peptide detection in disease models and clinical specimens. METHODS: We sought to detect p53 single amino acid variant (SAAV) peptides in breast cancer tumor samples that have been previously subjected to sequencing analysis...
February 3, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28155652/evaluating-the-effect-of-database-inflation-in-proteogenomic-search-on-sensitive-and-reliable-peptide-identification
#10
Honglan Li, Yoon Sung Joh, Hyunwoo Kim, Eunok Paek, Sang-Won Lee, Kyu-Baek Hwang
BACKGROUND: Proteogenomics is a promising approach for various tasks ranging from gene annotation to cancer research. Databases for proteogenomic searches are often constructed by adding peptide sequences inferred from genomic or transcriptomic evidence to reference protein sequences. Such inflation of databases has potential of identifying novel peptides. However, it also raises concerns on sensitive and reliable peptide identification. Spurious peptides included in target databases may result in underestimated false discovery rate (FDR)...
December 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28153736/proteogenomic-analysis-of-ncc-s1m-a-gastric-cancer-stem-cell-like-cell-line-that-responds-to-anti-pd-1
#11
Jun Won Park, Hyejin Um, Hanna Yang, Woori Ko, Dae-Yong Kim, Hark Kyun Kim
To elucidate signaling pathways that regulate gastric cancer stem cell (CSC) phenotypes and immune checkpoint, we performed a proteogenomic analysis of NCC-S1M, which is a gastric cancer cell line with CSC-like characteristics and is the only syngeneic gastric tumor cell line transplant model created in the scientific community. We found that the NCC-S1M allograft was responsive to anti-PD-1 treatment, and overexpressed Cd274 encoding PD-L1. PD-L1 was transcriptionally activated by loss of the TGF-β signaling...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28118949/a-golden-age-for-working-with-public-proteomics-data
#12
REVIEW
Lennart Martens, Juan Antonio Vizcaíno
Data sharing in mass spectrometry (MS)-based proteomics is becoming a common scientific practice, as is now common in the case of other, more mature 'omics' disciplines like genomics and transcriptomics. We want to highlight that this situation, unprecedented in the field, opens a plethora of opportunities for data scientists. First, we explain in some detail some of the work already achieved, such as systematic reanalysis efforts. We also explain existing applications of public proteomics data, such as proteogenomics and the creation of spectral libraries and spectral archives...
January 21, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28109431/proteogenomics-recycling-public-data-to-improve-genome-annotations
#13
A McAfee, L J Foster
Massively parallel sequencing is revealing species genomes faster than ever before, but the value of the raw sequence is limited unless the genes can be accurately annotated. This is typically achieved using gene prediction algorithms which, despite continual improvement, still require substantial verification and refinement. For example, in silico methods struggle with annotating splice isoforms accurately and empirical methods are needed to refine and verify the initial bioinformatic gene predictions. RNA-seq is an excellent way to confirm exon-exon boundaries and transcript termini, while mass spectrometry (MS) offers definitive proof that a gene is translated and a secondary means of confirming exon expression, protein termini, and posttranslational modifications...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28100699/proteogenomics-produces-comprehensive-and-highly-accurate-protein-coding-gene-annotation-in-a-complete-genome-assembly-of-malassezia-sympodialis
#14
Yafeng Zhu, Pär G Engström, Christian Tellgren-Roth, Charles D Baudo, John C Kennell, Sheng Sun, R Blake Billmyre, Markus S Schröder, Anna Andersson, Tina Holm, Benjamin Sigurgeirsson, Guangxi Wu, Sundar Ram Sankaranarayanan, Rahul Siddharthan, Kaustuv Sanyal, Joakim Lundeberg, Björn Nystedt, Teun Boekhout, Thomas L Dawson, Joseph Heitman, Annika Scheynius, Janne Lehtiö
Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28091603/repo-man-pp1-regulates-heterochromatin-formation-in-interphase
#15
Inês J de Castro, James Budzak, Maria L Di Giacinto, Lorena Ligammari, Ezgi Gokhan, Christos Spanos, Daniela Moralli, Christine Richardson, Jose I de Las Heras, Silvia Salatino, Eric C Schirmer, Katharine S Ullman, Wendy A Bickmore, Catherine Green, Juri Rappsilber, Sarah Lamble, Martin W Goldberg, Veronica Vinciotti, Paola Vagnarelli
Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Repo-Man, via Nup153, is enriched on condensed chromatin at the nuclear periphery and at the edge of the nucleopore basket. Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28031186/actg-novel-peptide-mapping-onto-gene-models
#16
Seunghyuk Choi, Hyunwoo Kim, Eunok Paek
In many proteogenomic applications, mapping peptide sequences onto genome sequences can be very useful, because it allows us to understand origins of the gene products. Existing software tools either take the genomic position of a peptide start site as an input or assume that the peptide sequence exactly matches the coding sequence of a given gene model. In case of novel peptides resulting from genomic variations, especially structural variations such as alternative splicing, these existing tools cannot be directly applied unless users supply information about the variant, either its genomic position or its transcription model...
December 28, 2016: Bioinformatics
https://www.readbyqxmd.com/read/28011598/reconstructing-metabolic-pathways-of-a-member-of-the-genus-pelotomaculum-suggesting-its-potential-to-oxidize-benzene-to-carbon-dioxide-with-direct-reduction-of-sulfate
#17
Xiyang Dong, Johannes Dröge, Christine von Toerne, Sviatlana Marozava, Alice C McHardy, Rainer U Meckenstock
The enrichment culture BPL is able to degrade benzene with sulfate as electron acceptor and is dominated by an organism of the genus Pelotomaculum Members of Pelotomaculum are usually known to be fermenters, undergoing syntrophy with anaerobic respiring microorganisms or methanogens. By using a metagenomic approach, we reconstructed a high-quality genome (∼2.97 Mbp, 99% completeness) for Pelotomaculum candidate BPL. The proteogenomic data suggested: (1) anaerobic benzene degradation was activated by a yet unknown mechanism for conversion of benzene to benzoyl-CoA; (2) the central benzoyl-CoA degradation pathway involved reductive dearomatization by a class II benzoyl-CoA reductase followed by hydrolytic ring cleavage and modified β-oxidation; (3) the oxidative acetyl-CoA pathway was utilized for complete oxidation to CO2 Interestingly, the genome of Pelotomaculum candidate BPL has all the genes for a complete sulfate reduction pathway including a similar electron transfer mechanism for dissimilatory sulfate reduction as in other Gram-positive sulfate-reducing bacteria...
December 22, 2016: FEMS Microbiology Ecology
https://www.readbyqxmd.com/read/28003436/integrating-transcriptomic-and-proteomic-data-for-accurate-assembly-and-annotation-of-genomes
#18
T S Keshava Prasad, Ajeet Kumar Mohanty, Manish Kumar, Sreelakshmi K Sreenivasamurthy, Gourav Dey, Raja Sekhar Nirujogi, Sneha M Pinto, Anil K Madugundu, Arun H Patil, Jayshree Advani, Srikanth S Manda, Manoj Kumar Gupta, Sutopa B Dwivedi, Dhanashree S Kelkar, Brantley Hall, Xiaofang Jiang, Ashley Peery, Pavithra Rajagopalan, Soujanya D Yelamanchi, Hitendra S Solanki, Remya Raja, Gajanan J Sathe, Sandip Chavan, Renu Verma, Krishna M Patel, Ankit P Jain, Nazia Syed, Keshava K Datta, Aafaque Ahmed Khan, Manjunath Dammalli, Savita Jayaram, Aneesha Radhakrishnan, Christopher J Mitchell, Chan-Hyun Na, Nirbhay Kumar, Photini Sinnis, Igor V Sharakhov, Charles Wang, Harsha Gowda, Zhijian Tu, Ashwani Kumar, Akhilesh Pandey
Complementing genome sequence with deep transcriptome and proteome data could enable more accurate assembly and annotation of newly sequenced genomes. Here, we provide a proof-of-concept of an integrated approach for analysis of the genome and proteome of Anopheles stephensi, which is one of the most important vectors of the malaria parasite. To achieve broad coverage of genes, we carried out transcriptome sequencing and deep proteome profiling of multiple anatomically distinct sites. Based on transcriptomic data alone, we identified and corrected 535 events of incomplete genome assembly involving 1196 scaffolds and 868 protein-coding gene models...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27988178/a-novel-protein-coding-potential-of-long-intergenic-non-coding-rnas-lincrnas-in-the-kinetoplastid-protozoan-parasite-leishmania-major
#19
Harsh Pawar, Kalpana Pai, Milind S Patole
Cutaneous leishmaniasis (CL) is caused by a kinetoplastid protozoan parasite Leishmania major, as a skin ulcer at the site of the sandfly bite. CL is curable and in most cases ulcers heal spontaneously within three to six months leaving a scar and disfiguration. Complete genome of L. major was reported in 2005 at the very initial phase of kinetoplastid parasite genome sequencing project. Presently, L. major genome is most studied and comprehensively annotated genome and therefore, it is being used as a reference genome for annotating recently sequenced Leishmanial genomes...
March 2017: Acta Tropica
https://www.readbyqxmd.com/read/27959540/unbiased-false-discovery-rate-estimation-for-shotgun-proteomics-based-on-the-target-decoy-approach
#20
Lev I Levitsky, Mark V Ivanov, Anna A Lobas, Mikhail V Gorshkov
Target-decoy approach (TDA) is the dominant strategy for false discovery rate (FDR) estimation in mass-spectrometry-based proteomics. One of its main applications is direct FDR estimation based on counting of decoy matches above a certain score threshold. The corresponding equations are widely employed for filtering of peptide or protein identifications. In this work we consider a probability model describing the filtering process and find that, when decoy counting is used for q value estimation and subsequent filtering, a correction has to be introduced into these common equations for TDA-based FDR estimation...
December 13, 2016: Journal of Proteome Research
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