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Bioinformatics & pathogenicity prediction

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https://www.readbyqxmd.com/read/29123525/identification-of-new-features-from-known-bacterial-protective-vaccine-antigens-enhances-rational-vaccine-design
#1
Edison Ong, Mei U Wong, Yongqun He
With many protective vaccine antigens reported in the literature and verified experimentally, how to use the knowledge mined from these antigens to support rational vaccine design and study underlying design mechanism remains unclear. In order to address the problem, a systematic bioinformatics analysis was performed on 291 Gram-positive and Gram-negative bacterial protective antigens with experimental evidence manually curated in the Protegen database. The bioinformatics analyses evaluated included subcellular localization, adhesin probability, peptide signaling, transmembrane α-helix and β-barrel, conserved domain, Clusters of Orthologous Groups, and Gene Ontology functional annotations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29111265/functional-assignment-for-essential-hypothetical-proteins-of-staphylococcus-aureus-n315
#2
Jyoti Prava, Pranavathiyani G, Archana Pan
Staphylococcus aureus, the causative agent of nosocomial infections worldwide, has acquired resistance to almost all antibiotics stressing the need to develop novel drugs against this pathogen. In S. aureus N315, 302 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 40 proteins encoded by S. aureus essential genes were found to be hypothetical and thus referred as essential hypothetical proteins (EHPs). The present study aims to carry out functional characterization of EHPs using bioinformatics tools/databases, whose performance was assessed by Receiver operating characteristic curve analysis...
October 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29110180/correlation-between-the-molecular-effects-of-mutations-at-the-dimer-interface-of-alanine-glyoxylate-aminotransferase-leading-to-primary-hyperoxaluria-type-i-and-the-cellular-response-to-vitamin-b6
#3
Mirco Dindo, Elisa Oppici, Daniele Dell'Orco, Rosa Montone, Barbara Cellini
Primary hyperoxaluria type I (PH1) is a rare disease caused by the deficit of liver alanine-glyoxylate aminotransferase (AGT). AGT prevents oxalate formation by converting peroxisomal glyoxylate to glycine. When the enzyme is deficient, progressive calcium oxalate stones deposit first in the urinary tract and then at the systemic level. Pyridoxal 5'-phosphate (PLP), the AGT coenzyme, exerts a chaperone role by promoting dimerization, as demonstrated by studies at protein and cellular level. Thus, variants showing a destabilized dimeric structure should, in principle, be responsive to vitamin B6, a precursor of PLP...
November 6, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29091310/design-of-inhibitory-peptide-targeting-toxoplasma-gondii-ron4-human-%C3%AE-tubulin-interactions-by-implementing-structural-bioinformatics-methods
#4
Umashankar Vetrivel, Hemavathy Nagarajan, Indhuja Thirumudi
Toxoplasma gondii an obligate intracellular parasite causes toxoplasmosis in homeothermic animals. Host invasion of this parasite is mediated by the formation of Moving Junction (MJ) complex which encompasses a network of microneme and Rhoptry Neck proteins (RONs) 2/4/5/8. Among these proteins, RON4 is the only cytosolic secretory protein that is considered as a crucial member, as it directly facilitates the motility of MJ complex by interacting with host tubulin. It is also prominently localised at the host-pathogen interface during the invasion, thus projecting it as a potential drug target...
November 1, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29091202/pointfinder-a-novel-web-tool-for-wgs-based-detection-of-antimicrobial-resistance-associated-with-chromosomal-point-mutations-in-bacterial-pathogens
#5
Ea Zankari, Rosa Allesøe, Katrine G Joensen, Lina M Cavaco, Ole Lund, Frank M Aarestrup
Background: Antibiotic resistance is a major health problem, as drugs that were once highly effective no longer cure bacterial infections. WGS has previously been shown to be an alternative method for detecting horizontally acquired antimicrobial resistance genes. However, suitable bioinformatics methods that can provide easily interpretable, accurate and fast results for antimicrobial resistance associated with chromosomal point mutations are still lacking. Methods: Phenotypic antimicrobial susceptibility tests were performed on 150 isolates covering three different bacterial species: Salmonella enterica, Escherichia coli and Campylobacter jejuni...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29077808/titindb-a-computational-tool-to-assess-titin-s-role-as-a-disease-gene
#6
Anna Laddach, Mathias Gautel, Franca Fraternali
Summary: Large numbers of rare and unique titin missense variants have been discovered in both healthy and disease cohorts, thus the correct classification of variants as pathogenic or non-pathogenic has become imperative. Due to titin's large size (363 coding exons), current web applications are unable to map titin variants to domain structures. Here, we present a web application, TITINdb, which integrates titin structure, variant, sequence and isoform information, along with pre-computed predictions of the impact of non-synonymous single nucleotide variants, to facilitate the correct classification of titin variants...
November 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29064633/proteomics-analysis-of-trichoplusia-ni-midgut-epithelial-cell-brush-border-membrane-vesicles
#7
Muhammad Afzal Javed, Cathy Coutu, David A Theilmann, Martin A Erlandson, Dwayne D Hegedus
The insect midgut epithelium is composed of columnar, goblet and regenerative cells. Columnar epithelial cells are the most abundant and have membrane protrusions that form the brush border membrane (BBM) on their apical side. These increase surface area available for the transport of nutrients, but also provide opportunities for interaction with xenobiotics such as pathogens, toxins and host plant allelochemicals. Recent improvements in proteomic and bioinformatics tools provided an opportunity to determine the proteome of the T...
October 24, 2017: Insect Science
https://www.readbyqxmd.com/read/29055967/reductive-evolution-in-outer-membrane-protein-biogenesis-has-not-compromised-cell-surface-complexity-in-helicobacter-pylori
#8
Chaille T Webb, Dilini Chandrapala, Siti Nurbaya Oslan, Rebecca S Bamert, Rhys D Grinter, Rhys A Dunstan, Rebecca J Gorrell, Jiangning Song, Richard A Strugnell, Trevor Lithgow, Terry Kwok
Helicobacter pylori is a gram-negative bacterial pathogen that chronically inhabits the human stomach. To survive and maintain advantage, it has evolved unique host-pathogen interactions mediated by Helicobacter-specific proteins in the bacterial outer membrane. These outer membrane proteins (OMPs) are anchored to the cell surface via a C-terminal β-barrel domain, which requires their assembly by the β-barrel assembly machinery (BAM). Here we have assessed the complexity of the OMP C-terminal β-barrel domains employed by H...
October 21, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/29044474/exome-sequencing-identifies-a-novel-nonsense-mutation-of-myo6-as-the-cause-of-deafness-in-a-brazilian-family
#9
Juliana Sampaio-Silva, Ana Carla Batissoco, Rafaela Jesus-Santos, Osório Abath-Neto, Luciano Cesar Scarpelli, Patricia Yoshie Nishimura, Layla Testa Galindo, Ricardo Ferreira Bento, Jeanne Oiticica, Karina Lezirovitz
We investigated 313 unrelated subjects who presented with hearing loss to identify the novel genetic causes of this condition in Brazil. Causative GJB2/GJB6 mutations were found in 12.7% of the patients. Among the familial cases (100/313), four were selected for exome sequencing. In one case, two novel heterozygous variants were found and were predicted to be pathogenic based on bioinformatics tools, that is, p.Ser906* (MYO6) and p.Arg42Cys (GJB3). We confirmed that this nonsense MYO6 mutation segregated with deafness in this family...
October 17, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/29039460/characterization-of-tree-shrew-tupaia-belangeri-interleukin-6-and-its-expression-pattern-in-response-to-exogenous-challenge
#10
Yuanyuan Han, Xiaomei Sun, Dexuan Kuang, Pinfen Tong, Caixia Lu, Wenguang Wang, Na Li, Yang Chen, Xiaoping Wang, Jiejie Dai, Huatang Zhang
Tree shrews, one of the closest relatives of primates, have attracted increasing attention as a model of human diseases, particularly for viral infections. As the first line of defense against microbial pathogens, the innate immune system is crucial in tree shrews. Interleukin-6 (IL-6) is important in the pathophysiology of infection, inflammation and cancer, where it promotes disease development or sustains immune reactions. The present study aimed to obtain further insight into the tree shrew IL-6 (tsIL-6) system, and the function of tsIL-6 in the antiviral and antibacterial response...
October 2, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29035294/predicting-amyloidogenic-proteins-in-the-proteomes-of-plants
#11
Kirill S Antonets, Anton A Nizhnikov
Amyloids are protein fibrils with characteristic spatial structure. Though amyloids were long perceived to be pathogens that cause dozens of incurable pathologies in humans and mammals, it is currently clear that amyloids also represent a functionally important form of protein structure implicated in a variety of biological processes in organisms ranging from archaea and bacteria to fungi and animals. Despite their social significance, plants remain the most poorly studied group of organisms in the field of amyloid biology...
October 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29034544/cyp2u1-activity-is-altered-by-missense-mutations-in-hereditary-spastic-paraplegia-56
#12
Christelle M Durand, Laura Dhers, Christelle Tesson, Alessandra Tessa, Laetitia Fouillen, Stéphanie Jacqueré, Laure Raymond, Isabelle Coupry, Giovanni Benard, Frédéric Darios, Khalid H El-Hachimi, Guja Astrea, François Rivier, Guillaume Banneau, Claire Pujol, Didier Lacombe, Alexandra Durr, Patrick J Babin, Filippo M Santorelli, Nicolas Pietrancosta, Jean-Luc Boucher, Daniel Mansuy, Giovanni Stevanin, Cyril Goizet
Hereditary Spastic Paraplegia (HSP) is an inherited disorder of the central nervous system mainly characterized by gradual spasticity and weakness of the lower limbs. SPG56 is a rare autosomal recessive early onset complicated form of HSP caused by mutations in CYP2U1. The CYP2U1 enzyme was shown to catalyze the hydroxylation of arachidonic acid. Here, we report two further SPG56 families carrying 3 novel CYP2U1 missense variants and the development of an in vitro biochemical assay to determine the pathogenicity of missense variants of uncertain clinical significance...
October 16, 2017: Human Mutation
https://www.readbyqxmd.com/read/29021397/varicella-zoster-virus-expresses-multiple-small-non-coding-rnas
#13
Amos Markus, Linoy Golani, Nishant Kumar Ojha, Tatiana Borodiansky-Shteinberg, Paul R Kinchington, Ronald S Goldstein
Many herpesviruses express small non coding RNAs (sncRNA), including microRNAs (miR), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella zoster virus (VZV, HHV-3). Here we analyzed next generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20-24 nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRs...
October 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28981926/-genetic-and-prenatal-diagnosis-of-a-pedigree-affected-with-type-3-von-willebrand-disease
#14
Haiyan Zhu, Chunyan Ji
OBJECTIVE: To provide genetic and prenatal analysis for a pedigree affected with type 3 von Willebrand disease. METHODS: Next generation sequencing and Sanger sequencing of the VWF gene were carried out for the pedigree. Suscepted pathogenic mutation was verified among other members of the pedigree and 100 healthy controls. Prenatal diagnosis was performed on amniotic cells derived from the fetus. RESULTS: A homozygous mutation c.7287+1G>A of the VWF gene was detected in the patient, which was predicted by bioinformatic analysis as a pathological splice site mutation...
October 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28981473/novel-eda-or-edar-mutations-identified-in-patients-with-x-linked-hypohidrotic-ectodermal-dysplasia-or-non-syndromic-tooth-agenesis
#15
Binghui Zeng, Qi Zhao, Sijie Li, Hui Lu, Jiaxuan Lu, Lan Ma, Wei Zhao, Dongsheng Yu
Abstract: Both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic tooth agenesis (NSTA) result in symptoms of congenital tooth loss. This study investigated genetic causes in two families with XLHED and four families with NSTA. We screened for mutations of WNT10A, EDA, EDAR, EDARADD, PAX9, MSX1, AXIN2, LRP6, and WNT10B through Sanger sequencing. Whole exome sequencing was performed for the proband of NSTA Family 4. Novel mutation c.1051G>T (p.Val351Phe) and the known mutation c.467G>A (p...
October 5, 2017: Genes
https://www.readbyqxmd.com/read/28968714/fathmm-xf-accurate-prediction-of-pathogenic-point-mutations-via-extended-features
#16
Mark F Rogers, Hashem A Shihab, Matthew Mort, David N Cooper, Tom R Gaunt, Colin Campbell
Summary: We present FATHMM-XF , a method for predicting pathogenic point mutations in the human genome. Drawing on an extensive feature set, FATHMM-XF outperforms competitors on benchmark tests, particularly in non-coding regions where the majority of pathogenic mutations are likely to be found. Availability: The FATHMM-XF web server is available at http://fathmm.biocompute.org.uk/fathmm-xf/ , and as tracks on the Genome Tolerance Browser: http://gtb.biocompute...
September 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28961796/in-silico-identification-of-rescue-sites-by-double-force-scanning
#17
Matteo Tiberti, Alessandro Pandini, Franca Fraternali, Arianna Fornili
Motivation: A deleterious amino acid change in a protein can be compensated by a second-site rescue mutation. These compensatory mechanisms can be mimicked by drugs. In particular, the location of rescue mutations can be used to identify protein regions that can be targeted by small molecules to reactivate a damaged mutant. Results: We present the first general computational method to detect rescue sites. By mimicking the effect of mutations through the application of forces, the Double Force Scanning (DFS) method identifies the second-site residues that make the protein structure most resilient to the effect of pathogenic mutations...
August 14, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28959259/transmembrane-helices-are-an-overlooked-source-of-major-histocompatibility-complex-class-i-epitopes
#18
Frans Bianchi, Johannes Textor, Geert van den Bogaart
About a fourth of the human proteome is anchored by transmembrane helices (TMHs) to lipid membranes. TMHs require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I. It, therefore, comes as no surprise that bioinformatics analysis predicts an over-representation of TMHs among strong MHC class I (MHC-I) binders. Published peptide elution studies confirm that TMHs are indeed presented by MHC-I...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28959245/phylogenomic-pan-genomic-pathogenomic-and-evolutionary-genomic-insights-into-the-agronomically-relevant-enterobacteria-pantoea-ananatis-and-pantoea-stewartii
#19
Pieter De Maayer, Habibu Aliyu, Surendra Vikram, Jochen Blom, Brion Duffy, Don A Cowan, Theo H M Smits, Stephanus N Venter, Teresa A Coutinho
Pantoea ananatis is ubiquitously found in the environment and causes disease on a wide range of plant hosts. By contrast, its sister species, Pantoea stewartii subsp. stewartii is the host-specific causative agent of the devastating maize disease Stewart's wilt. This pathogen has a restricted lifecycle, overwintering in an insect vector before being introduced into susceptible maize cultivars, causing disease and returning to overwinter in its vector. The other subspecies of P. stewartii subsp. indologenes, has been isolated from different plant hosts and is predicted to proliferate in different environmental niches...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28957710/two-s-company-studying-interspecies-relationships-with-dual-rna-seq
#20
REVIEW
Thomas Wolf, Philipp Kämmer, Sascha Brunke, Jörg Linde
Organisms do not exist isolated from each other, but constantly interact. Cells can sense the presence of interaction partners by a range of receptors and, via complex regulatory networks, specifically react by changing the expression of many of their genes. Technological advances in next-generation sequencing over the recent years now allow us to apply RNA sequencing to two species at the same time (dual RNA-seq), and thus to directly study the gene expression of two interacting species without the need to physically separate cells or RNA...
September 25, 2017: Current Opinion in Microbiology
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