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Translational bioinformatics

Violeta Muñoz-Fuentes, Pilar Cacheiro, Terrence F Meehan, Juan Antonio Aguilar-Pimentel, Steve D M Brown, Ann M Flenniken, Paul Flicek, Antonella Galli, Hamed Haseli Mashhadi, Martin Hrabě de Angelis, Jong Kyoung Kim, K C Kent Lloyd, Colin McKerlie, Hugh Morgan, Stephen A Murray, Lauryl M J Nutter, Patrick T Reilly, John R Seavitt, Je Kyung Seong, Michelle Simon, Hannah Wardle-Jones, Ann-Marie Mallon, Damian Smedley, Helen E Parkinson
The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and phenotyping a knockout mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species...
2018: Conservation Genetics
Gurpreet Kaur, Pratap Kumar Pati
BACKGROUND: NADPH oxidase (Nox) is a critical enzyme involved in the generation of apoplastic superoxide (O2 - ), a type of reactive oxygen species (ROS) and hence regulate a wide range of biological functions in many organisms. Plant Noxes are the homologs of the catalytic subunit from mammalian NADPH oxidases and are known as respiratory burst oxidase homologs (Rbohs). Previous studies have highlighted their versatile roles in tackling different kind of stresses and in plant growth and development...
August 10, 2018: BMC Plant Biology
Panagiotis G Adamopoulos, Christos K Kontos, Marios A Diamantopoulos, Andreas Scorilas
The adaptor-related protein (AP) complexes play important roles in cargo selection and vesicle formation, and hence in intracellular membrane trafficking. Five different AP complexes are currently known, each consisting of four subunits, known as adaptins. AP-2, the most thoroughly characterized of the five AP complexes, facilitates clathrin-mediated endocytosis. In this study, we describe the discovery and molecular cloning of seventy-seven novel alternatively spliced transcripts of the human AP2A1 gene, which encodes the αA adaptin of the AP-2 complex...
August 3, 2018: Gene
Setareh Ghavami, Hassan Toozandehjani, Ghazaleh Ghavami, Soroush Sardari
One of the valuable bioinformatics techniques is protein sequence alignment which is a method of searching, comparing and ordering the sequences of protein. The pointed method is employed to recognize region of similarity which may be a significance of functional, structural, or evolutionary relatives between the protein sequences. In current investigation, an innovative similarity search/alignment algorithm for pattern recognition process of protein structures in the frame of bio-mimicking pattern recognition capabilities of human visual and auditory systems towards investigating more and more novel approaches in the field of protein sequence alignment procedure...
August 1, 2018: International Journal of Biological Macromolecules
Patrycja Sosińska-Zawierucha, Piotr Zawierucha, Andrzej Bręborowicz, Jan Barciszewski
Based on experimental and bioinformatic approaches we present the first empirically established complete secondary structure of human BC200 RNA. BC200 RNA is a brain- specific non-messenger RNA with a confirmed regulatory role in dendritic translation in neurons. Although the involvement of human BC200 RNA in various types of tumour and Alzheimer's disease has been repeatedly confirmed, the exact secondary structure remains not fully elucidated. In order to determine the secondary structure of BC200 RNA in vitro , we performed partially hydrolysis with sequence-specific nucleases and lead-induced cleavage...
August 2, 2018: Biochemical Journal
Victoria Torrance, David Lydall
The levels of telomeric proteins, such as telomerase, can have profound effects on telomere function, cell division and human disease. Here we demonstrate how levels of Stn1, a component of the conserved telomere capping CST (Cdc13, Stn1, Ten1) complex, are tightly regulated by an upstream overlapping open reading frame (oORF). In budding yeast inactivation of the STN1 oORF leads to a 10-fold increase in Stn1 levels, reduced telomere length, suppression of cdc13-1 and enhancement of yku70Δ growth defects. The STN1 oORF impedes translation of the main ORF and reduces STN1 mRNA via the nonsense mediated mRNA decay (NMD) pathway...
August 1, 2018: PLoS Genetics
Krishna Kanhaiya, Vladimir Rogojin, Keivan Kazemi, Eugen Czeizler, Ion Petre
BACKGROUND: Network controllability focuses on discovering combinations of external interventions that can drive a biological system to a desired configuration. In practice, this approach translates into finding a combined multi-drug therapy in order to induce a desired response from a cell; this can lead to developments of novel therapeutic approaches for systemic diseases like cancer. RESULT: We develop a novel bioinformatics data analysis pipeline called NetControl4BioMed based on the concept of target structural control of linear networks...
July 9, 2018: BMC Bioinformatics
Antonino Fiannaca, Laura La Paglia, Massimo La Rosa, Giosue' Lo Bosco, Giovanni Renda, Riccardo Rizzo, Salvatore Gaglio, Alfonso Urso
BACKGROUND: An open challenge in translational bioinformatics is the analysis of sequenced metagenomes from various environmental samples. Of course, several studies demonstrated the 16S ribosomal RNA could be considered as a barcode for bacteria classification at the genus level, but till now it is hard to identify the correct composition of metagenomic data from RNA-seq short-read data. 16S short-read data are generated using two next generation sequencing technologies, i.e. whole genome shotgun (WGS) and amplicon (AMP); typically, the former is filtered to obtain short-reads belonging to a 16S shotgun (SG), whereas the latter take into account only some specific 16S hypervariable regions...
July 9, 2018: BMC Bioinformatics
Claudia Matteucci, Ayele Argaw-Denboba, Emanuela Balestrieri, Alessandro Giovinazzo, Martino Miele, Cartesio D'Agostini, Francesca Pica, Sandro Grelli, Maurizio Paci, Antonio Mastino, Paola Sinibaldi Vallebona, Enrico Garaci, Carlo Tomino
BACKGROUND: Thymosin alpha 1 (Tα1) is a well-recognized immune response modulator in a wide range of disorders, particularly infections and cancer. The bioinformatic analysis of public databases allows drug repositioning, predicting a new potential area of clinical intervention. We aimed to decipher the cellular network induced by Tα1 treatment to confirm present use and identify new potential clinical applications. RESEARCH DESIGN AND METHODS: We used the transcriptional profile of human peripheral blood mononuclear cells treated in vitro with Tα1 to perform the enrichment network analysis by the Metascape online tools and the disease enrichment analysis by the DAVID online tool...
July 2018: Expert Opinion on Biological Therapy
Sylvester M Greer, Simone Sidoli, Mariel Coradin, Malena Schack Jespersen, Veit Schwämmle, Ole Nørregaard Jensen, Benjamin A Garcia, Jennifer S Brodbelt
The ability to map combinatorial patterns of post-translational modifications (PTMs) of proteins remains challenging for traditional bottom-up mass spectrometry workflows. There are also hurdles associated with top-down approaches related to limited data analysis options for heavily modified proteoforms. These shortcomings have accelerated interest in middle-down MS methods that focus on analysis of large peptides generated by specific proteases in conjunction with validated bioinformatics strategies to allow quantification of isomeric histoforms...
July 31, 2018: Analytical Chemistry
H J Bolz
Until the mid-2000s, knowledge about the genetic causes of retinal dystrophies was not adequately translated into molecular diagnostics and genetic counselling offered to the patients. Although many genes whose mutations underlie retinal degeneration, e.g., retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophies were known, they could not be analyzed on a routine diagnostic basis because DNA sequencing was too expensive and time-consuming. New methods summarized under the term next-generation sequencing (NGS) procedures for high-throughput sequencing have changed this completely...
July 27, 2018: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
Ashraful Arefeen, Juntao Liu, Xinshu Xiao, Tao Jiang
Motivation: The length of the 3' untranslated region (3' UTR) of an mRNA is essential for many biological activities such as mRNA stability, sub-cellular localization, protein translation, protein binding and translation efficiency. Moreover, correlation between diseases and the shortening (or lengthening) of 3' UTRs has been reported in the literature. This length is largely determined by the polyadenylation cleavage site in the mRNA. As alternative polyadenylation (APA) sites are common in mammalian genes, several tools have been published recently for detecting APA sites from RNA-Seq data or performing shortening/lengthening analysis...
August 1, 2018: Bioinformatics
Shahideh Nouri, Emilyn E Matsumura, Yen-Wen Kuo, Bryce W Falk
Over the past decade the scientific community has experienced a new age of virus discovery in arthropods in general, and in insects in particular. Next generation sequencing and advanced bioinformatics tools have provided new insights about insect viromes and viral evolution. In this review, we discuss some high-throughput sequencing technologies used to discover viruses in insects and the challenges raised in data interpretations. Additionally, the discovery of these novel viruses that are considered as insect-specific viruses (ISVs) has gained increasing attention in their potential use as biological agents...
July 23, 2018: Current Opinion in Virology
Elena Fountzilas, Apostolia M Tsimberidou
Introduction In recent years, the therapeutic management of selected patients with cancer has shifted towards the 'Precision Medicine" approach based on patient's mechanisms of tumorigenesis, and their baseline characteristics and comorbidities. Complete tumor and cell-free DNA profiling using next-generation sequencing, proteomic and RNA analysis, and immune mechanisms should to be taken into consideration and accurate bioinformatic analysis is essential to optimize patient's treatment. Areas covered The challenges and opportunities of conducting clinical trials in precision oncology are summarized...
July 25, 2018: Expert Review of Clinical Pharmacology
Xiaojing Tian, Qianqian Yu, Wei Wu, Xingmin Li, Ruitong Dai
Escherichia coli O157:H7 is an important food-borne pathogenic microorganism that has been used as a model organism for studying microbial inactivation effects and inactivation mechanism in various sterilization technologies. The objective of this study was to investigate the effects of high voltage short time ohmic- (HVST), low voltage long time ohmic- (LVLT), and water bath- (WB) heating on inactivation and proteome changes of E. coli O157:H7 cells at the same endpoint temperature of 72 °C, and to analyze whether a non-thermal death effect existed in ohmic heating...
June 8, 2018: International Journal of Food Microbiology
Qi Zhao, Yue Zhang, Huan Hu, Guofei Ren, Wen Zhang, Hongsheng Liu
Long non-coding RNA (lncRNA) plays an important role in many important biological processes and has attracted widespread attention. Although the precise functions and mechanisms for most lncRNAs are still unknown, we are certain that lncRNAs usually perform their functions by interacting with the corresponding RNA- binding proteins. For example, lncRNA-protein interactions play an important role in post transcriptional gene regulation, such as splicing, translation, signaling, and advances in complex diseases...
2018: Frontiers in Genetics
Simon Hsu, Brian A Gordon, Russ Hornbeck, Joanne B Norton, Denise Levitch, Adia Louden, Ellen Ziegemeier, Robert Laforce, Jasmeer Chhatwal, Gregory S Day, Eric McDade, John C Morris, Anne M Fagan, Tammie L S Benzinger, Alison M Goate, Carlos Cruchaga, Randall J Bateman, Celeste M Karch
BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that is clinically characterized by progressive cognitive decline. Mutations in amyloid-β precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the pathogenic cause of autosomal dominant AD (ADAD). However, polymorphisms also exist within these genes. METHODS: In order to distinguish polymorphisms from pathogenic mutations, the DIAN Expanded Registry has implemented an algorithm for determining ADAD pathogenicity using available information from multiple domains, including genetic, bioinformatic, clinical, imaging, and biofluid measures and in vitro analyses...
July 18, 2018: Alzheimer's Research & Therapy
Junfeng Zhang, Liping He, Yougen Wu, Wentin Ma, He Chen, Zhouchen Ye
A proteomic approach was used to understand the molecular mechanisms underlying obstacles to the continuous cropping of Pogostemon cablin. We examined differences in protein abundance between control (CK) and continuously cropped (TR) P. cablin leaves at different time points (90, 150, and 210 days after culture). Comparative analysis by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) revealed 183 differentially expressed protein spots, of which 87 proteins or isoforms were identified using mass spectrometry...
July 12, 2018: Protein Expression and Purification
Weiwei Fu, Ningbo Chen, Shuang Han, Jieping Huang, Fen Li, Ruijie Hao, Hong Chen, Chuzhao Lei, Yun Ma
Adipokines play a crucial role in the regulation of energy homeostasis; however, little is known about genetic alterations in this family that may contribute to economic traits in cattle. Therefore, this study conducts transcript profiles, variations and association studies of three major adipokines, leptin (LEP), tumour necrosis factor (TNF) and angiopoietin-like protein 8 (ANGPTL8), to evaluate their effects on native Chinese cattle. Using quantitative real-time PCR, the study revealed that the bovine LEP was expressed primarily in the back and visceral fat, while TNF was predominantly expressed in spleen and ANGPTL8 was mainly expressed in back fat and liver...
July 16, 2018: Reproduction in Domestic Animals, Zuchthygiene
Venkatramanan Krishnamani, Tabitha A Peterson, Robert C Piper, Mark A Stamnes
We have adapted the yeast 2-hybrid assay to simultaneously uncover dozens of transient and static protein interactions within a single screen utilizing high-throughput short-read DNA sequencing. The resulting sequence datasets can not only track what genes in a population that are enriched during selection for positive yeast 2-hybrid interactions, but also give detailed information about the relevant subdomains of proteins sufficient for interaction. Here, we describe a full suite of stand-alone software programs that allow non-experts to perform all the bioinformatics and statistical steps to process and analyze DNA sequence fastq files from a batch yeast 2-hybrid assay...
June 28, 2018: Journal of Visualized Experiments: JoVE
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