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Tomer Meirson, Alessandro Genna, Nikola Lukic, Tetiana Makhnii, Joel Alter, Ved P Sharma, Yarong Wang, Abraham O Samson, John S Condeelis, Hava Gil-Henn
Metastatic dissemination of cancer cells from the primary tumor and their spread to distant sites in the body is the leading cause of mortality in breast cancer patients. While researchers have identified treatments that shrink or slow metastatic tumors, no treatment that permanently eradicates metastasis exists at present. Here, we show that the ABL kinase inhibitors imatinib, nilotinib, and GNF-5 impede invadopodium precursor formation and cortactin-phosphorylation dependent invadopodium maturation, leading to decreased actin polymerization in invadopodia, reduced extracellular matrix degradation, and impaired matrix proteolysis-dependent invasion...
April 24, 2018: Oncotarget
Yafeng Zhu, Lukas M Orre, Henrik J Johansson, Mikael Huss, Jorrit Boekel, Mattias Vesterlund, Alejandro Fernandez-Woodbridge, Rui M M Branca, Janne Lehtiö
In the original version of this Article, extraneous text not belonging to the Article was accidentally appended to the results section. This error has now been corrected in both the PDF and HTML versions of the Article.
May 8, 2018: Nature Communications
Sonam Vijay, Ritu Rawal, Kavita Kadian, Jagbir Singh, Tridibesh Adak, Arun Sharma
BACKGROUND: Midgut invasion, a major bottleneck for malaria parasites transmission is considered as a potential target for vector-parasite interaction studies. New intervention strategies are required to explore the midgut proteins and their potential role in refractoriness for malaria control in Anopheles mosquitoes. To better understand the midgut functional proteins of An. culicifacies susceptible and refractory species, proteomic approaches coupled with bioinformatics analysis is an effective means in order to understand the mechanism of refractoriness...
May 8, 2018: BMC Genomics
Anne J Kleinnijenhuis, Frédérique L van Holthoon
Collagen is an important structural protein and the most abundant protein in mammals. In several research fields, structural analysis of collagens is performed. Fibrillar collagens almost entirely consist of continuous repeats of GXY, where G is glycine, X is often proline or alanine and Y is often hydroxyproline or alanine. In the present study, the collagen structure was investigated in detail at the nucleotide, codon group, amino acid and target peptide level using sequence analyses. One of the most important findings was that a selection of codon groups is predominantly involved in amino acid changes between closely related collagens and that other change routes come up when collagens are less related...
May 2, 2018: Journal of Molecular Evolution
Wei Zhao, Jun Li, Rehan Akbani, Han Liang, Gordon B Mills
An integrated analysis of DNA, RNA and protein, so called proteogenomic studies, has the potential to greatly increase our understanding of both normal physiology and disease development. However, such studies are challenged by a lack of a systematic approach to credential individual samples resulting in the introduction of noise into the system that limits the ability to identify important biological signals. Indeed, a recent proteogenomic CPTAC study identified 26% of samples as unsatisfactory, resulting in a marked increase in cost and loss of information content...
May 1, 2018: Molecular & Cellular Proteomics: MCP
Petra Pjevac, Dimitri V Meier, Stephanie Markert, Christian Hentschker, Thomas Schweder, Dörte Becher, Harald R Gruber-Vodicka, Michael Richter, Wolfgang Bach, Rudolf Amann, Anke Meyerdierks
At hydrothermal vent sites, chimneys consisting of sulfides, sulfates, and oxides are formed upon contact of reduced hydrothermal fluids with oxygenated seawater. The walls and surfaces of these chimneys are an important habitat for vent-associated microorganisms. We used community proteogenomics to investigate and compare the composition, metabolic potential and relative in situ protein abundance of microbial communities colonizing two actively venting hydrothermal chimneys from the Manus Basin back-arc spreading center (Papua New Guinea)...
2018: Frontiers in Microbiology
Paula Moolhuijzen, Pao Theen See, James K Hane, Gongjun Shi, Zhaohui Liu, Richard P Oliver, Caroline S Moffat
BACKGROUND: Pyrenophora tritici-repentis (Ptr) is a necrotrophic fungal pathogen that causes the major wheat disease, tan spot. We set out to provide essential genomics-based resources in order to better understand the pathogenicity mechanisms of this important pathogen. RESULTS: Here, we present eight new Ptr isolate genomes, assembled and annotated; representing races 1, 2 and 5, and a new race. We report a high quality Ptr reference genome, sequenced by PacBio technology with Illumina paired-end data support and optical mapping...
April 23, 2018: BMC Genomics
Henry Rodriguez, Stephen R Pennington
The integration of proteomics into precision oncology presents opportunities that may transform the molecular analysis of cancer and accelerate basic and clinical cancer research. This Commentary discusses the importance of international collaboration and data sharing inspired by the Cancer Moonshot to accelerate the progress of multi-omic precision medicine-an approach that addresses the global diversity of people and of cancers.
April 19, 2018: Cell
S A Moshkovskii, M V Ivanov, K G Kuznetsova, M V Gorshkov
An important aim of proteogenomics, which combines data of high throughput nucleic acid and protein analysis, is to reliably identify single amino acid substitutions representing a main type of coding genome variants. Exact knowledge of deviations from the consensus genome can be utilized in several biomedical fields, such as studies of expression of mutated proteins in cancer, deciphering heterozygosity mechanisms, identification of neoantigens in anticancer vaccine production, search for RNA editing sites at the level of the proteome, etc...
March 2018: Biochemistry. Biokhimii︠a︡
Anna A Lobas, Mikhail A Pyatnitskiy, Alexey L Chernobrovkin, Irina Y Ilina, Dmitry S Karpov, Elizaveta M Solovyeva, Ksenia G Kuznetsova, Mark V Ivanov, Elena Y Lyssuk, Anna A Kliuchnikova, Olga E Voronko, Sergey S Larin, Roman A Zubarev, Mikhail V Gorshkov, Sergei A Moshkovskii
Identification of genetically encoded variants at the proteome level is an important problem in cancer proteogenomics. Generation of customized protein databases from DNA or RNA sequencing data is a crucial stage of the identification workflow. Genomic data filtering applied at this stage may significantly modify variant search results, yet its effect is generally left out of the scope of proteogenomic studies. In this work, we focused on this impact using data of exome sequencing and LC-MS/MS analyses of six replicates for eight melanoma cell lines processed by a proteogenomics workflow...
April 5, 2018: Journal of Proteome Research
Seyed Yahya Anvar, Guy Allard, Elizabeth Tseng, Gloria M Sheynkman, Eleonora de Klerk, Martijn Vermaat, Raymund H Yin, Hans E Johansson, Yavuz Ariyurek, Johan T den Dunnen, Stephen W Turner, Peter A C 't Hoen
BACKGROUND: The multifaceted control of gene expression requires tight coordination of regulatory mechanisms at transcriptional and post-transcriptional level. Here, we studied the interdependence of transcription initiation, splicing and polyadenylation events on single mRNA molecules by full-length mRNA sequencing. RESULTS: In MCF-7 breast cancer cells, we find 2700 genes with interdependent alternative transcription initiation, splicing and polyadenylation events, both in proximal and distant parts of mRNA molecules, including examples of coupling between transcription start sites and polyadenylation sites...
March 29, 2018: Genome Biology
Jiao Ma, Alan Saghatelian, Maxim Nikolaievich Shokhirev
Proteogenomics methods have identified many non-annotated protein-coding genes in the human genome. Many of the newly discovered protein-coding genes encode peptides and small proteins, referred to collectively as microproteins. Microproteins are produced through ribosome translation of small open reading frames (smORFs). The discovery of many smORFs reveals a blind spot in traditional gene-finding algorithms for these genes. Biological studies have found roles for microproteins in cell biology and physiology, and the potential that there exists additional bioactive microproteins drives the interest in detection and discovery of these molecules...
2018: PloS One
Sabrina Bibi-Triki, Gauthier Husson, Bruno Maucourt, Stéphane Vuilleumier, Christine Carapito, Françoise Bringel
Methylobacterium strains can use one-carbon compounds, such as methanol, for methylotrophic growth. In addition to methanol, a few strains also utilize dichloromethane, a major industrial chlorinated solvent pollutant. With a fully assembled and annotated genome, M. extorquens DM4 is the reference bacterium for aerobic dichloromethane degradation. The doublet N-terminal oriented proteomics (dN-TOP) strategy was applied to further improve its genome annotation and a differential proteomics approach was performed to compare M...
March 19, 2018: Journal of Proteomics
Leena Latonen, Ebrahim Afyounian, Antti Jylhä, Janika Nättinen, Ulla Aapola, Matti Annala, Kati K Kivinummi, Teuvo T L Tammela, Roger W Beuerman, Hannu Uusitalo, Matti Nykter, Tapio Visakorpi
To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes...
March 21, 2018: Nature Communications
Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark K 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 2691 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...
April 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, as well as 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, 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 is carried out...
February 22, 2018: Proteomics. Clinical Applications
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