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Translational bioinformatics

Omran Abu Aboud, Robert H Weiss
In the age of bioinformatics and with the advent of high-powered computation over the past decade or so the landscape of biomedical research has become radically altered. Whereas a generation ago, investigators would study their "favorite" protein or gene and exhaustively catalog the role of this compound in their disease of interest, the appearance of omics has changed the face of medicine such that much of the cutting edge (and fundable!) medical research now evaluates the biology of the disease nearly in its entirety...
November 27, 2017: Kidney cancer
Jason R Phillips, Daniel L Svoboda, Arpit Tandon, Shyam Patel, Alex Sedykh, Deepak Mav, Byron Kuo, Carole L Yauk, Longlong Yang, Russell S Thomas, Jeff S Gift, J Allen Davis, Louis Olysyzk, B Alex Merrick, Richard S Paules, Fred Parham, Trey Saddler, Ruchir R Shah, Scott S Auerbach
Summary: A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses the increasing use of transcriptomic dose-response data in toxicology, drug design, risk assessment, and translational research. In this new version, we have implemented additional statistical filtering options (e.g., Williams' trend test), curve fitting models, Linux and Macintosh compatibility, and support for additional transcriptomic platforms with up-to-date gene annotations...
October 17, 2018: Bioinformatics
Qiao Sun, Weijun Wang, Lifang Wu, Lu Cheng, Xuemei Tong, Xun Xu
PURPOSE: To identify the clinical characteristics and pathogenic genes among a Chinese family with angioid streaks and to assess a novel splicing mutation at the transcriptional and translational levels. METHODS: Consenting family members were clinically evaluated, and blood samples were collected for targeted exome capture sequencing and/or Sanger sequencing. The two affected siblings were assessed by multimodal fundus imaging. ABCC6 splicing patterns were analysed by RNA identification and quantification using the proband's peripheral blood mononuclear cells...
October 17, 2018: Acta Ophthalmologica
Soumyadip Paul, Suvranil Ghosh, Sukhendu Mandal, Subrata Sau, Mahadeb Pal
Functional up-regulation of heat shock factor 1 (HSF1) activity through different post-translational modifications has been implicated in the survival and proliferation of various cancers. It is increasingly recognized that the HSF1 gene is also up-regulated at the transcriptional level, a phenomenon correlated with poor prognosis for patients with different cancers, including breast cancer. Here, we analyzed the transcriptional up-regulation of HSF1 in human cells upon arsenite- or peroxide-induced oxidative stress...
October 11, 2018: Journal of Biological Chemistry
Sophie Paczesny, Jochen Metzger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy...
October 11, 2018: Proteomics. Clinical Applications
Kasey Jividen, Katarzyna Z Kedzierska, Chun-Song Yang, Karol Szlachta, Aakrosh Ratan, Bryce M Paschal
BACKGROUND: The cellular effects of androgen are transduced through the androgen receptor, which controls the expression of genes that regulate biosynthetic processes, cell growth, and metabolism. Androgen signaling also impacts DNA damage signaling through mechanisms involving gene expression and transcription-associated DNA damaging events. Defining the contributions of androgen signaling to DNA repair is important for understanding androgen receptor function, and it also has translational implications...
October 10, 2018: BMC Cancer
Dengke Zhao, William Baez, Kurt Fredrick, Ralf Bundschuh
Motivation: Ribosome profiling has been widely used to study translation in a genome-wide fashion. It requires deep sequencing of ribosome protected mRNA fragments followed by mapping of fragments to the reference genome. For applications such as identification of ribosome pausing sites, it is not enough to map a fragment to a given gene, but the exact position of the ribosome represented by the fragment must be identified for each mRNA fragment. The assignment of the correct ribosome position is complicated by the broad length distribution of the ribosome protected fragments caused by the known sequence bias of micrococcal nuclease (MNase), the most widely used nuclease for digesting mRNAs in bacteria...
October 10, 2018: Bioinformatics
Michael K Hjortness, Laura Riccardi, Akarawin Hongdusit, Peter H Zwart, Banumathi Sankaran, Marco De Vivo, Jerome M Fox
Protein tyrosine phosphatases (PTPs) are an important class of regulatory enzymes that exhibit aberrant activities in a wide range of diseases. A detailed mapping of allosteric communication in these enzymes could, thus, reveal the structural basis of physiologically relevant-and, perhaps, therapeutically informative-perturbations (i.e., mutations, post-translational modifications, or binding events) that influence their catalytic states. This study combines detailed biophysical studies of protein tyrosine phosphatase 1B (PTP1B) with bioinformatic analyses of the PTP family to examine allosteric communication in PTPs...
October 5, 2018: Biochemistry
Zhen Chen, Xuhan Liu, Fuyi Li, Chen Li, Tatiana Marquez-Lago, André Leier, Tatsuya Akutsu, Geoffrey I Webb, Dakang Xu, Alexander Ian Smith, Lei Li, Kuo-Chen Chou, Jiangning Song
Lysine post-translational modifications (PTMs) play a crucial role in regulating diverse functions and biological processes of proteins. However, because of the large volumes of sequencing data generated from genome-sequencing projects, systematic identification of different types of lysine PTM substrates and PTM sites in the entire proteome remains a major challenge. In recent years, a number of computational methods for lysine PTM identification have been developed. These methods show high diversity in their core algorithms, features extracted and feature selection techniques and evaluation strategies...
October 4, 2018: Briefings in Bioinformatics
Patricia Sampaio Tavares Veras, Pablo Ivan Pereira Ramos, Juliana Perrone Bezerra de Menezes
Leishmaniasis is a vector-borne, neglected tropical disease with a worldwide distribution that can present in a variety of clinical forms, depending on the parasite species and host genetic background. The pathogenesis of this disease remains far from being elucidated because the involvement of a complex immune response orchestrated by host cells significantly affects the clinical outcome. Among these cells, macrophages are the main host cells, produce cytokines and chemokines, thereby triggering events that contribute to the mediation of the host immune response and, subsequently, to the establishment of infection or, alternatively, disease control...
2018: Frontiers in Cellular and Infection Microbiology
Angeles Aroca, Cecilia Gotor, Luis C Romero
Hydrogen sulfide (H2 S) has been largely referred as a toxic gas and environmental hazard, but recent years, it has emerged as an important gas-signaling molecule with effects on multiple physiological processes in both animal and plant systems. The regulatory functions of H2 S in plants are involved in important processes such as the modulation of defense responses, plant growth and development, and the regulation of senescence and maturation. The main signaling pathway involving sulfide has been proven to be through protein persulfidation (alternatively called S- sulfhydration), in which the thiol group of cysteine (-SH) in proteins is modified into a persulfide group (-SSH)...
2018: Frontiers in Plant Science
Jenelle A Patterson, Ian J Tetlow, Michael J Emes
Starch synthase 2 (SS2) is an important enzyme in leaf starch synthesis, elongating intermediate-length glucan chains. Loss of SS2 results in a distorted starch granule phenotype and altered physiochemical properties, highlighting its importance in starch biosynthesis, however, the post-translational regulation of SS2 is poorly understood. In this study, a combination of bioinformatic and in vitro analysis of recombinant SS2 was used to identify and characterize SS2 post-translational regulatory mechanisms...
2018: Frontiers in Plant Science
Markus Heinonen, Fabien Milliat, Mohamed Amine Benadjaoud, Agnès François, Valérie Buard, Georges Tarlet, Florence d'Alché-Buc, Olivier Guipaud
The vascular endothelium is considered as a key cell compartment for the response to ionizing radiation of normal tissues and tumors, and as a promising target to improve the differential effect of radiotherapy in the future. Following radiation exposure, the global endothelial cell response covers a wide range of gene, miRNA, protein and metabolite expression modifications. Changes occur at the transcriptional, translational and post-translational levels and impact cell phenotype as well as the microenvironment by the production and secretion of soluble factors such as reactive oxygen species, chemokines, cytokines and growth factors...
2018: PloS One
Ritu Rawal, Sonam Vijay, Kavita Kadian, Tridibesh Adak, Veena Pande, Arun Sharma
Background & objectives: Salivary gland proteins play a pivotal role in blood feeding, epithelial interactions, and parasite transmission in mosquito vectors. Anopheles culicifacies is a complex of five sibling species, viz. A, B, C, D, and E, with diverse geographical distribution patterns. Among these, sibling species B has been identified as poor vector. Exploring the differentially expressed salivary proteins in An. culicifacies may potentially identify refractoriness factors during malaria parasite maturation and may help to elucidate the mechanism of refractoriness...
April 2018: Journal of Vector Borne Diseases
Mary Regan, Mary B Engler, Bernice Coleman, Sandra Daack-Hirsch, Kathleen A Calzone
PURPOSE: To establish the knowledge needed to integrate the multiple branches of omics into nursing research to accelerate achieving the research recommendations of the Genomic Nursing Science Blueprint. METHODS: The creation of the Genomic Knowledge Matrix occurred in three phases. In phase 1, the Omics Nursing Science and Education Network (ONSEN) Education Workgroup completed an evidence, bioinformatics, and technology review to inform the components of the Matrix...
October 1, 2018: Journal of Nursing Scholarship
Turner A Conrad, Chien-Chi Lo, Jeffrey W Koehler, Amanda S Graham, Christopher P Stefan, Adrienne T Hall, Christina E Douglas, Patrick Sam Guy Chain, Timothy D Minogue
Next-generation sequencing (NGS) for infectious disease diagnostics is a relatively new and under-developed concept. If this technology is to become a regulatory-grade clinical diagnostic, standardization in the form of locked-down assays and firmly established underlying processes is necessary. Targeted sequencing, specifically by amplification of genomic signatures, has the potential to bridge the gap between PCR- and NGS-based diagnostics; however, existing NGS assay panels lack validated analytical techniques to adjudicate high background and error prone NGS data...
September 27, 2018: Journal of Molecular Diagnostics: JMD
Yu-Pu Liu, Peng Xu, Chun-Xia Guo, Zhi-Rong Luo, Jing Zhu, Fang-Fang Mou, Hao Cai, Chang Wang, Xiao-Chun Ye, Shui-Jin Shao, Hai-Dong Guo
Peripheral nerve injury (PNI) is a global problem that leads to severe disability and high healthcare expenditure. Accumulating evidence suggested that the phenotypes of Schwann cells (SCs) could be regulated by microRNAs (miRNAs) and expressions of various miRNAs are altered after PNI. In this study, the expression of miR-1b in the injured nerve and hypoxia-treated SCs was detected through qRT-PCR. The target genes of miR-1b were predicted by bioinformatics prediction and dual-luciferase reporter assay and verified through qRT-PCR and western blot...
September 24, 2018: Neuroscience Letters
Tian He, Karen McColl, Nneha Sakre, Yanwen Chen, Gary Wildey, Afshin Dowlati
Protein Inhibitor of Activated STAT3 (PIAS3) is an endogenous suppressor of Signal Transducer and Activator of Transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper-activated in various cancers. We previously reported that in malignant mesothelioma (MM), low PIAS3 expression is associated with increased STAT3 activation and correlates with poor patient survival, yet the regulatory mechanism(s) governing PIAS3 expression in MM remain unclear...
September 27, 2018: Molecular Oncology
Amaresh Chandra Panda
Majority of RNAs expressed in animal cells lack protein-coding ability. Unlike other cellular RNAs, circular (circ)RNAs include a large family of noncoding (nc)RNAs that lack the 5' or 3' ends. The improvements in high-throughput RNA sequencing and novel bioinformatics tools have led to the identification of thousands of circRNAs in various organisms. CircRNAs can regulate gene expression by influencing the transcription, the mRNA turnover, and translation by sponging RNA-binding proteins and microRNAs. Given the broad impact of circRNA on miRNA activity, there is huge interest in understanding the impact of miRNA sponging by circRNA on gene regulation...
2018: Advances in Experimental Medicine and Biology
Marco Trevisan-Herraz, Navratan Bagwan, Fernando García-Marqués, Jose Manuel Rodriguez, Inmaculada Jorge, Iakes Ezkurdia, Elena Bonzon-Kulichenko, Jesús Vázquez
Summary: Mass spectrometry-based proteomics has had a formidable development in recent years, increasing the amount of data handled and the complexity of the statistical resources needed. Here we present SanXoT, an open-source, standalone software package for the statistical analysis of high-throughput, quantitative proteomics experiments. SanXoT is based on our previously developed WSPP statistical model and has been specifically designed to be modular, scalable, and user-configurable...
September 25, 2018: Bioinformatics
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