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Translational bioinformatics

Urszula Kaźmierczak, Małgorzata Kwaśniak-Owczarek
The ribosome profiling approach (Ribo-seq) is currently the most effective method to study the protein synthesis in vivo. This technique relies on sequencing of ribosome protected mRNA fragments (so-called ribosomal footprints) allowing to indicate the exact positions of ribosomes on transcripts. Advanced bioinformatic analysis of Ribo-seq data enables selection of ribosomal footprints originated from translating ribosomes, providing information about authentic translational status of mRNA. Here, authors present principles of ribosome profiling method with special attention to basic experimental and bioinformatics strategies important for obtaining satisfactory results...
March 22, 2019: Postepy Biochemii
Mihir R Atreya, Hector R Wong
PURPOSE OF REVIEW: Pediatric sepsis is a heterogeneous state associated with significant morbidity and mortality, but treatment strategies are limited. Clinical trials of immunomodulators in sepsis have shown no benefit, despite having a strong biological rationale. There is considerable interest in application of a precision medicine approach to pediatric sepsis to identify patients who are more likely to benefit from targeted therapeutic interventions. RECENT FINDINGS: Precision medicine requires a clear understanding of the molecular basis of disease...
March 18, 2019: Current Opinion in Pediatrics
Bohu Pan, Rebecca Kusko, Wenming Xiao, Yuanting Zheng, Zhichao Liu, Chunlin Xiao, Sugunadevi Sakkiah, Wenjing Guo, Ping Gong, Chaoyang Zhang, Weigong Ge, Leming Shi, Weida Tong, Huixiao Hong
BACKGROUND: Reference genome selection is a prerequisite for successful analysis of next generation sequencing (NGS) data. Current practice employs one of the two most recent human reference genome versions: HG19 or HG38. To date, the impact of genome version on SNV identification has not been rigorously assessed. METHODS: We conducted analysis comparing the SNVs identified based on HG19 vs HG38, leveraging whole genome sequencing (WGS) data from the genome-in-a-bottle (GIAB) project...
March 14, 2019: BMC Bioinformatics
Q Miao, Z Zhong, Z Jiang, Y Lin, B Ni, W Yang, J Tang
BACKGROUND: Circular RNAs (circRNAs) are possible biomarkers for many diseases, but the knowledge of circRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) remains limited. This study aimed to assess the expression of circRNAs in PBMCs from patients with SLE and healthy individuals by RNA sequencing (RNA-seq). METHODS: In total, 128 circRNAs were significantly differentially expressed including 39 upregulated and 89 downregulated circRNAs in four new-onset SLE patients compared with three healthy controls...
March 14, 2019: Lupus
Chenliang Yu, Qinqfei Wu, Chendong Sun, Mengling Tang, Junwei Sun, Yihua Zhan
Soil salinization is a major environmental stresses that seriously threatens land use efficiency and crop yields worldwide. Although the overall response of plants to NaCl has been well studied, the contribution of protein phosphorylation to the detoxification and tolerance of NaCl in okra ( Abelmoschus esculentus L.) seedlings is unclear. The molecular bases of okra seedlings' responses to 300 mM NaCl stress are discussed in this study. Using a combination of affinity enrichment, tandem mass tag (TMT) labeling and high-performance liquid chromatography⁻tandem mass spectrometry analysis, a large-scale phosphoproteome analysis was performed in okra...
March 13, 2019: International Journal of Molecular Sciences
Jiaxin Liu, Zhao Liu, Xiaozhi Zhang, Tuotuo Gong, Demao Yao
BACKGROUND: Gastric cancer (GC) is one of the most commonly occuring gastrointestinal tumor types, and early diagnosis and operation have a notable effect on the prognosis of patients. Although certain markers, including HER2, VEGER-2, ERCC1 and Bcl-2, have been utilized in clinical practise to screen out new patients with GC, the results of using these markers remains poor. The role of olfactomedin-like 2B (OLFML2B) in GC, as a member of the olfactomedin domain-containing proteins family, is remain unclear...
March 13, 2019: BMC Cancer
Ho Jang, Hyunju Lee
MOTIVATION: Whole-genome sequencing (WGS) data are affected by various sequencing biases such as GC bias and mappability bias. These biases degrade performance on detection of genetic variations such as copy number alterations. The existing methods use a relation between the GC proportion and depth of coverage (DOC) of markers by means of regression models. Nonetheless, severity of the GC bias varies from sample to sample. We developed a new method for correction of GC bias on the basis of multiresolution analysis...
March 13, 2019: Bioinformatics
Mariam M Al Eissa, Sally I Sharp, Niamh L O'Brien, Alessia Fiorentino, Nicholas J Bass, David Curtis, Andrew McQuillin
A rare microcephalin 1 gene (MCPH1) variant rs61749465A>G (p.Asp61Gly) with prior evidence for association with schizophrenia (p = 3.78 × 10-7 ) was tested for association in 2,300 bipolar disorder (BPD) participants, 1,930 SCZ participants and 1,820 normal comparison subjects. We report evidence for association of rs61749465A>G with BPD (p = 0.0009). rs61749465 is located in the N-terminal of the BRCT1 domain of MCPH1. Bioinformatic analysis predicted the Asp61Gly substitution to be damaging to MCPH1 function...
March 11, 2019: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Karoline Kollmann, Coralie Briand, Florian Bellutti, Nikolaus Schicher, Stefan Blunder, Markus Zojer, Christoph Hoeller
The cyclin-dependent kinases CDK4 and CDK6 promote progression through the cell cycle, where their functions are considered to be redundant. Recent studies have identified an additional role for CDK6 in the transcriptional regulation of cancer-relevant genes such as VEGF-A and EGR1 in hematopoietic malignancies. We show that the CDK4/6 inhibitor PD0332991 causes a significant decrease in tumor growth in a xenotransplantation mouse model of human melanoma. shRNA knockdown of either CDK4 or CDK6 significantly reduces cell proliferation and impedes their migratory capacity in vitro , which translates into a strong inhibition of tumor growth in xenotransplantation experiments...
February 15, 2019: Oncotarget
Wei Yan, Shawn Xiang Li, Hongyu Gao, Wei Yang
B-cell translocation gene 1 (BTG1) is a member of the BTG/transducer of Erb family. The present study evaluated the impact of BTG1 gene expression on the clinical outcome of diffuse large B-cell lymphoma (DLBCL) and investigated potential mechanisms using the Gene Expression Omnibus (GEO) database. The gene expression profile datasets GSE31312, GSE10846, GSE65420 and GSE87371 were downloaded from the GEO database. BTG1 expression and clinicopathological data were obtained from the GSE31312 dataset. In 498 cases, the expression of BTG1 in DLBCL was associated with treatment response (χ2 =19...
March 2019: Oncology Letters
Yanfang Wang, Shan Xin, Kai Zhang, Run Shi, Xuanwen Bao
Introduction: Gliomas are infiltrative neoplasms of a highly invasive nature. Different stages of gliomas feature distinct genomic, genetic, and epigenetic changes. The long noncoding RNA Growth Arrest Specific Transcript 5 (GAS5) is an identified tumour suppressor involved in several cancers. However, the underlying roles of the GAS5 gene in lower-grade glioma (LGG) patients are not clear. Methods: Via bioinformatic analysis based on TCGA-LGG and TCGA-GBM data, we explored the mechanisms of GAS5 expression in LGG (grades II and III) and high-grade glioma (glioblastoma multiforme, grade IV)...
2019: Journal of Oncology
Tsung-Ming Chen, Ming-Chih Lai, Yi-Han Li, Ya-Ling Chan, Chih-Hao Wu, Yu-Ming Wang, Chun-Wei Chien, San-Yuan Huang, H Sunny Sun, Shaw-Jenq Tsai
BACKGROUND: Hypoxia suppresses global protein production, yet certain essential proteins are translated through alternative pathways to survive under hypoxic stress. Translation via the internal ribosome entry site (IRES) is a means to produce proteins under stress conditions such as hypoxia; however, the underlying mechanism remains largely uncharacterized. METHODS: Proteomic and bioinformatic analyses were employed to identify hnRNPM as an IRES interacting factor...
March 6, 2019: EBioMedicine
S P McGovern, D C Purfield, S C Ring, T R Carthy, D A Graham, D P Berry
Infection of cattle with bovine paratuberculosis (i.e., Johne's disease) is caused by Mycobacterium avium subspecies paratuberculosis (MAP) and results in a chronic incurable gastroenteritis. This disease, which has economic ramifications for the cattle industry, is increasing in detected prevalence globally; subclinically infected animals can silently shed the bacterium into the environment for years, exposing contemporaries and hampering disease-control programs. The objective of the present study was to first quantify the genetic parameters for humoral response to MAP in dairy cattle...
March 6, 2019: Journal of Dairy Science
Yan Liu, Ning Dong, Jiyu Miao, Chenxing Li, Xiaofei Wang, Jianping Ruan
Caries, pulpitis, and trauma are the main causes of dental pulp damage. The regeneration capacity of dental pulp declines with age. Lin28 is a conserved RNA-binding protein in higher eukaryotes that regulates several important cellular functions associated with development, glucose metabolism, differentiation, and pluripotency. Conditional reactivation of Lin28 gene in adult mice markedly accelerates the wound-healing process in injured digits. However, little is known about its functions and molecular mechanism in human dental pulp...
March 6, 2019: Biomedicine & Pharmacotherapy
Ehsaneddin Asgari, Alice C McHardy, Mohammad R K Mofrad
In this paper, we present peptide-pair encoding (PPE), a general-purpose probabilistic segmentation of protein sequences into commonly occurring variable-length sub-sequences. The idea of PPE segmentation is inspired by the byte-pair encoding (BPE) text compression algorithm, which has recently gained popularity in subword neural machine translation. We modify this algorithm by adding a sampling framework allowing for multiple ways of segmenting a sequence. PPE segmentation steps can be learned over a large set of protein sequences (Swiss-Prot) or even a domain-specific dataset and then applied to a set of unseen sequences...
March 5, 2019: Scientific Reports
Jeremy Weaver, Fuad Mohammad, Allen R Buskirk, Gisela Storz
Small proteins consisting of 50 or fewer amino acids have been identified as regulators of larger proteins in bacteria and eukaryotes. Despite the importance of these molecules, the total number of small proteins remains unknown because conventional annotation pipelines usually exclude small open reading frames (smORFs). We previously identified several dozen small proteins in the model organism Escherichia coli using theoretical bioinformatic approaches based on sequence conservation and matches to canonical ribosome binding sites...
March 5, 2019: MBio
Yuqing Hao, Merve Kacal, Amanda Tomie Ouchida, Boxi Zhang, Erik Norberg, Helin Vakifahmetoglu-Norberg
Chaperone-mediated autophagy is a lysosomal degradation pathway of select soluble proteins. Nearly one-third of the soluble proteins are predicted to be recognized by this pathway, yet only a minor fraction of this proteome has been identified as CMA substrates in cancer cells. Here, we undertook a quantitative multiplex mass spectrometry approach to study the proteome of isolated lysosomes in cancer cells during CMA-activated conditions. By integrating bioinformatics analyses, we identified and categorized proteins of multiple cellular pathways that were specifically targeted by CMA...
March 1, 2019: Autophagy
Luca Falzone, Giovanni L Romano, Rossella Salemi, Claudio Bucolo, Barbara Tomasello, Gabriella Lupo, Carmelina D Anfuso, Demetrios A Spandidos, Massimo Libra, Saverio Candido
Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high‑risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high‑grade vs...
February 11, 2019: Molecular Medicine Reports
Ying Jian Chen, Yuan Jun Liao, Fan Lin, Shen Gnan Sun, Xiao Lei Zhao, Ji Heng Qin, Shao Qi Rao
Although nasopharyngeal carcinoma (NPC) and oral squamous cell carcinoma (OSCC) are highly correlated clinical diseases, the underling molecular mechanisms to link the two diseases remain largely unknown. The aim of this study is to identify the shared functional modules for NPC and OSCC by using large-scale transcriptomic data. Gene expression profile datasets of NPC and OSCC were obtained from the GEO database. A total of 1279 differentially expressed genes (DEGs) of NPC and 1293 DEGs of OSCC were identified by fold change and empirical Bayes method, and 278 DEGs were common to these two diseases...
February 20, 2019: Yi Chuan, Hereditas
Chaoyong Tu, Wei Chen, Shuqian Wang, Wei Tan, Jingqiang Guo, Chuxiao Shao, Weilin Wang
Drug resistance occurs commonly in cancers, especially in hepatocellular carcinoma (HCC). Accumulating evidence has demonstrated that microRNAs (miRNAs) play a vital role in tumour chemoresistance. However, little is known about the role of miR-383 in HCC chemoresistance. In the present study, RT-PCR and western blotting were used to identify the expression profile of miR-383 and eukaryotic translation initiation factor 5A2 (EIF5A2). The bioinformatics website Targetscan was used to predict the target genes of miR-383...
February 23, 2019: Journal of Cellular and Molecular Medicine
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