Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimüllerian hormone expression during oocyte maturation in the female follicle.

Wnt4 is a key signal that channels the developmental fate of the indifferent mammalian gonad toward the ovary, but whether Wnt4 has later roles during ovary development remains unknown. To investigate this, we inactivated the Wnt4 gene by crossing Amhr2Cre and doxycycline-inducible Rosa(rtTA)-knock-in Cre mice with mice carrying a floxed Wnt4 allele and used a novel Wnt4(mCherry)-knock-in mouse. In these models, ovarian folliculogenesis was compromised, and female fertility was severely reduced, and Wnt4 deficiency eventually led to premature ovarian failure.

Molecular dynamic simulation to explore the molecular basis of Btk-PH domain interaction with Ins(1,3,4,5)P4.

Bruton's tyrosine kinase contains a pleckstrin homology domain, and it specifically binds inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), which is involved in the maturation of B cells. In this paper, we studied 12 systems including the wild type and 11 mutants, K12R, S14F, K19E, R28C/H, E41K, L11P, F25S, Y40N, and K12R-R28C/H, to investigate any change in the ligand binding site of each mutant. Molecular dynamics simulations combined with the method of molecular mechanics/Poisson-Boltzmann solvent-accessible surface area have been applied to the twelve systems, and reasonable mutant structures and their binding free energies have been obtained as criteria in the final classification.

SVR_CAF: an integrated score function for detecting native protein structures among decoys.

An accurate score function for detecting the most native-like models among a huge number of decoy sets is essential to the protein structure prediction. In this work, we developed a novel integrated score function (SVR_CAF) to discriminate native structures from decoys, as well as to rank near-native structures and select best decoys when native structures are absent. SVR_CAF is a machine learning score, which incorporates the contact energy based score (CE_score), amino acid network based score (AAN_score), and the fast Fourier transform based score (FFT_score).

Diagnosis value of the serum amyloid A test in neonatal sepsis: a meta-analysis.

Neonatal sepsis (NS), a common disorder for humans, is recognized as a leading global public health challenge. This meta-analysis was performed to assess the accuracy of the serum amyloid A (SAA) test for diagnosing NS. The studies that evaluated the SAA test as a diagnostic marker were searched in Pubmed, EMBASE, the Cochrane Library, and Google Network between January 1996 and June 2013.

Translational bioinformatics for diagnostic and prognostic prediction of prostate cancer in the next-generation sequencing era.

The discovery of prostate cancer biomarkers has been boosted by the advent of next-generation sequencing (NGS) technologies. Nevertheless, many challenges still exist in exploiting the flood of sequence data and translating them into routine diagnostics and prognosis of prostate cancer. Here we review the recent developments in prostate cancer biomarkers by high throughput sequencing technologies.

Clear cell renal cell carcinoma associated microRNA expression signatures identified by an integrated bioinformatics analysis.

Background: Clear cell renal cell carcinoma (ccRCC) represents the most invasive and common adult kidney neoplasm. Mounting evidence suggests that microRNAs (miRNAs) are important regulators of gene expression. But their function in tumourigenesis in this tumour type remains elusive.

Translational biomedical informatics in the cloud: present and future.

Next generation sequencing and other high-throughput experimental techniques of recent decades have driven the exponential growth in publicly available molecular and clinical data. This information explosion has prepared the ground for the development of translational bioinformatics. The scale and dimensionality of data, however, pose obvious challenges in data mining, storage, and integration.

Genome-scale analysis of the metabolic networks of oleaginous Zygomycete fungi.

Microbial lipids are becoming an attractive option for the industrial production of foods and oleochemicals. To investigate the lipid physiology of the oleaginous microorganisms, at the system level, genome-scale metabolic networks of Mortierella alpina and Mucor circinelloides were constructed using bioinformatics and systems biology. As scaffolds for integrated data analysis focusing on lipid production, consensus metabolic routes governing fatty acid synthesis, and lipid storage and mobilisation were identified by comparative analysis of developed metabolic networks.

The topology and dynamics of protein complexes: insights from intra- molecular network theory.

Intra-molecular interactions within complex systems play a pivotal role in the biological function. They form a major challenge to computational structural proteomics. The network paradigm treats any system as a set of nodes linked by edges corresponding to the relations existing between the nodes.

Molecular signature of cancer at gene level or pathway level? Case studies of colorectal cancer and prostate cancer microarray data.

With recent advances in microarray technology, there has been a flourish in genome-scale identification of molecular signatures for cancer. However, the differentially expressed genes obtained by different laboratories are highly divergent. The present discrepancy at gene level indicates a need for a novel strategy to obtain more robust signatures for cancer.

Identification and functional annotation of genome-wide ER-regulated genes in breast cancer based on ChIP-Seq data.

Estrogen receptor (ER) is a crucial molecule symbol of breast cancer. Molecular interactions between ER complexes and DNA regulate the expression of genes responsible for cancer cell phenotypes. However, the positions and mechanisms of the ER binding with downstream gene targets are far from being fully understood.

Biomedical text mining and its applications in cancer research.

Cancer is a malignant disease that has caused millions of human deaths. Its study has a long history of well over 100years. There have been an enormous number of publications on cancer research.

Structure-based prediction of the effects of a missense variant on protein stability.

Predicting the effects of amino acid substitutions on protein stability provides invaluable information for protein design, the assignment of biological function, and for understanding disease-associated variations. To understand the effects of substitutions, computational models are preferred to time-consuming and expensive experimental methods. Several methods have been proposed for this task including machine learning-based approaches.

The preservation of bidirectional promoter architecture in eukaryotes: what is the driving force?

Background: The bidirectional gene architecture has been studied in many organisms, and the conservation of bidirectional arrangement has received considerable attention. However, the explanation for the evolutionary conservation about this genomic structure is still insufficient. In this study the large scale identification and pathway enrichment analysis for bidirectional genes were performed in several eukaryotes and the comparative analysis of this arrangement between human and mouse were dissected for the purpose of discovering the driving force of the preservation of this genomic structure.

Combined SVM-CRFs for biological named entity recognition with maximal bidirectional squeezing.

Biological named entity recognition, the identification of biological terms in text, is essential for biomedical information extraction. Machine learning-based approaches have been widely applied in this area. However, the recognition performance of current approaches could still be improved.

A systems biology perspective on rational design of peptide vaccine against virus infections.

With the recent onset of influenza A (H1N1) pandemic, the need for improved vaccines against virus infections has become an international priority. Strategies for vaccine development have changed over time, from whole-virus to immunogenic proteins and further to antigenic viral peptides. Various algorithms and bioinformatics tools have been developed to predict immunogenic peptide regions in an antigenic protein sequence.

Investigation of the acetylation mechanism by GCN5 histone acetyltransferase.

The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation and motility. Of the enzymes that mediate post-translation modifications, the GCN5 of the histone acetyltransferase (HAT) proteins family that add acetyl groups to target lysine residues within histones, has been most extensively studied. According to the mechanism studies of GCN5 related proteins, two key processes, deprotonation and acetylation, must be involved.

Performance comparison and evaluation of software tools for microRNA deep-sequencing data analysis.

With the development of next-generation sequencing (NGS) techniques, many software tools have emerged for the discovery of novel microRNAs (miRNAs) and for analyzing the miRNAs expression profiles. An overall evaluation of these diverse software tools is lacking. In this study, we evaluated eight software tools based on their common feature and key algorithms.

Review of computer-aided models for predicting collagen stability.

Collagen is the most abundant protein in the whole human body and its instability is involved in many important diseases, such as Osteogenesis imperfecta, Ehlers-Danlos syndrome, and collagenopathy. The stability of the collagen triple helix is strictly related to its amino acid sequence, especially the main Gly-X-Y motif. Many groups have used computational methods to investigate collagen's structure and the relationship between its stability and structure.

Catalytic mechanism investigation of lysine-specific demethylase 1 (LSD1): a computational study.

Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a flavin-dependent amine oxidase which specifically demethylates mono- or dimethylated H3K4 and H3K9 via a redox process. It participates in a broad spectrum of biological processes and is of high importance in cell proliferation, adipogenesis, spermatogenesis, chromosome segregation and embryonic development. To date, as a potential drug target for discovering anti-tumor drugs, the medical significance of LSD1 has been greatly appreciated.

Origination of new immunological functions in the costimulatory molecule B7-H3: the role of exon duplication in evolution of the immune system.

B7-H3, a recently identified B7 family member, has different isoforms in human and mouse. Mouse B7-H3 gene has only one isoform (2IgB7-H3) with two Ig-like domains, whereas human B7-H3 has two isoforms (2IgB7-H3 and 4IgB7-H3). In this study a systematic genomic survey across various species from teleost fishes to mammals revealed that 4IgB7-H3 isoform also appeared in pigs, guinea pigs, cows, dogs, African elephants, pandas, megabats and higher primate animals, which resulted from tandem exon duplication.

Identifying novel prostate cancer associated pathways based on integrative microarray data analysis.

The development and diverse application of microarray and next generation sequencing technologies has made the meta-analysis widely used in expression data analysis. Although it is commonly accepted that pathway, network and systemic level approaches are more reproducible than reductionism analyses, the meta-analysis of prostate cancer associated molecular signatures at the pathway level remains unexplored. In this article, we performed a meta-analysis of 10 prostate cancer microarray expression datasets to identify the common signatures at both the gene and pathway levels.

Genome-wide analysis of the transcription factor binding preference of human bi-directional promoters and functional annotation of related gene pairs.

Background: Bi-directional gene pairs have received considerable attention for their prevalence in vertebrate genomes. However, their biological relevance and exact regulatory mechanism remain less understood. To study the inner properties of this gene organization and the difference between bi- and uni-directional genes, we conducted a genome-wide investigation in terms of their sequence composition, functional association and regulatory motif discovery.