Regulation of retinal amacrine cell generation by miR-216b and Foxn3.

The mammalian retina contains a complex mixture of different types of neurons. We find that microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b directed the formation of additional amacrine cells and reduced bipolar neurons in the developing retina.

Phage display broadly identifies inhibitor-reactive regions in von Willebrand factor.

Background: Correction of von Willebrand factor (VWF) deficiency with replacement products containing VWF can lead to the development of anti-VWF alloantibodies (i.e., VWF inhibitors) in patients with severe von Willebrand disease (VWD).

microRNA-mRNA Profile of Skeletal Muscle Differentiation and Relevance to Congenital Myotonic Dystrophy.

microRNAs (miRNAs) regulate messenger RNA (mRNA) abundance and translation during key developmental processes including muscle differentiation. Assessment of miRNA targets can provide insight into muscle biology and gene expression profiles altered by disease. mRNA and miRNA libraries were generated from C2C12 myoblasts during differentiation, and predicted miRNA targets were identified based on presence of miRNA binding sites and reciprocal expression.

Rapid molecular assays to study human centromere genomics.

The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time.

The microRNA network is altered in anterior cingulate cortex of patients with unipolar and bipolar depression.

MicroRNAs (miRNAs) are small, non-coding RNAs acting as post-transcriptional regulators of gene expression. Though implicated in multiple CNS disorders, miRNAs have not been examined in any psychiatric disease state in anterior cingulate cortex (AnCg), a brain region centrally involved in regulating mood. We performed qPCR analyses of 29 miRNAs previously implicated in psychiatric illness (major depressive disorder (MDD), bipolar disorder (BP) and/or schizophrenia (SZ)) in AnCg of patients with MDD and BP versus controls.

Massively parallel enzyme kinetics reveals the substrate recognition landscape of the metalloprotease ADAMTS13.

Proteases play important roles in many biologic processes and are key mediators of cancer, inflammation, and thrombosis. However, comprehensive and quantitative techniques to define the substrate specificity profile of proteases are lacking. The metalloprotease ADAMTS13 regulates blood coagulation by cleaving von Willebrand factor (VWF), reducing its procoagulant activity.

Human Endogenous Retrovirus Type K (HERV-K) Particles Package and Transmit HERV-K-Related Sequences.

Unlabelled: Human endogenous retroviruses (HERV) make up 8% of the human genome. While the youngest of these retroviruses, HERV-K(HML-2), termed HK2, is able to code for all viral proteins and produce virus-like particles, it is not known if these virus particles package and transmit HK2-related sequences. Here, we analyzed the capacity of HK2 for packaging and transmitting HK2 sequences.

Regulation of the human endogenous retrovirus K (HML-2) transcriptome by the HIV-1 Tat protein.

Unlabelled: Approximately 8% of the human genome is made up of endogenous retroviral sequences. As the HIV-1 Tat protein activates the overall expression of the human endogenous retrovirus type K (HERV-K) (HML-2), we used next-generation sequencing to determine which of the 91 currently annotated HERV-K (HML-2) proviruses are regulated by Tat. Transcriptome sequencing of total RNA isolated from Tat- and vehicle-treated peripheral blood lymphocytes from a healthy donor showed that Tat significantly activates expression of 26 unique HERV-K (HML-2) proviruses, silences 12, and does not significantly alter the expression of the remaining proviruses.

G protein-linked signaling pathways in bipolar and major depressive disorders.

The G-protein linked signaling system (GPLS) comprises a large number of G-proteins, G protein-coupled receptors (GPCRs), GPCR ligands, and downstream effector molecules. G-proteins interact with both GPCRs and downstream effectors such as cyclic adenosine monophosphate (cAMP), phosphatidylinositols, and ion channels. The GPLS is implicated in the pathophysiology and pharmacology of both major depressive disorder (MDD) and bipolar disorder (BPD).

HIV infection reveals widespread expansion of novel centromeric human endogenous retroviruses.

Human endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV-K (HML-2) family is the most recent group of these viruses to have inserted into the genome, and we have detected the activation of HERV-K (HML-2) proviruses in the blood of patients with HIV-1 infection. We report that HIV-1 infection activates expression of a novel HERV-K (HML-2) provirus, termed K111, present in multiple copies in the centromeres of chromosomes throughout the human genome yet not annotated in the most recent human genome assembly.

Impact of experimental noise and annotation imprecision on data quality in microarray experiments.

Data quality is intrinsically influenced by design, technical, and analytical parameters. Quality parameters have not yet been well defined for gene expression analysis by microarrays, though ad interim, following recommended good experimental practice guidelines should ensure generation of reliable and reproducible data. Here we summarize essential practical recommendations for experimental design, technical considerations, feature annotation issues, and standardization efforts.

NGSQC: cross-platform quality analysis pipeline for deep sequencing data.

Background: While the accuracy and precision of deep sequencing data is significantly better than those obtained by the earlier generation of hybridization-based high throughput technologies, the digital nature of deep sequencing output often leads to unwarranted confidence in their reliability.

Results: The NGSQC (Next Generation Sequencing Quality Control) pipeline provides a set of novel quality control measures for quickly detecting a wide variety of quality issues in deep sequencing data derived from two dimensional surfaces, regardless of the assay technology used. It also enables researchers to determine whether sequencing data related to their most interesting biological discoveries are caused by sequencing quality issues.

Cross-domain neurobiology data integration and exploration.

Background: Understanding the biomedical implications of data from high throughput experiments requires solutions for effective cross-scale and cross-domain data exploration. However, existing solutions do not provide sufficient support for linking molecular level data to neuroanatomical structures, which is critical for understanding high level neurobiological functions.

Results: Our work integrates molecular level data with high level biological functions and we present results using anatomical structure as a scaffold.

Open Biomedical Ontology-based Medline exploration.

Background: Effective Medline database exploration is critical for the understanding of high throughput experimental results and the development of novel hypotheses about the mechanisms underlying the targeted biological processes. While existing solutions enhance Medline exploration through different approaches such as document clustering, network presentations of underlying conceptual relationships and the mapping of search results to MeSH and Gene Ontology trees, we believe the use of multiple ontologies from the Open Biomedical Ontology can greatly help researchers to explore literature from different perspectives as well as to quickly locate the most relevant Medline records for further investigation.

Results: We developed an ontology-based interactive Medline exploration solution called PubOnto to enable the interactive exploration and filtering of search results through the use of multiple ontologies from the OBO foundry.

A diagram editor for efficient biomedical knowledge capture and integration.

Understanding the molecular mechanisms underlying complex disorders requires the integration of data and knowledge from different sources including free text literature and various biomedical databases. To facilitate this process, we created the Biomedical Concept Diagram Editor (BCDE) to help researchers distill knowledge from data and literature and aid the process of hypothesis development. A key feature of BCDE is the ability to capture information with a simple drag-and-drop.

Supercomputing with toys: harnessing the power of NVIDIA 8800GTX and playstation 3 for bioinformatics problem.

Modern video cards and game consoles typically have much better performance to price ratios than that of general purpose CPUs. The parallel processing capabilities of game hardware are well-suited for high throughput biomedical data analysis. Our initial results suggest that game hardware is a cost-effective platform for some computationally demanding bioinformatics problems.

An active visual search interface for Medline.

Searching the Medline database is almost a daily necessity for many biomedical researchers. However, available Medline search solutions are mainly designed for the quick retrieval of a small set of most relevant documents. Because of this search model, they are not suitable for the large-scale exploration of literature and the underlying biomedical conceptual relationships, which are common tasks in the age of high throughput experimental data analysis and cross-discipline research.

Web-based GeneChip analysis system for large-scale collaborative projects.

Unlabelled: The Web-Based GeneChip Analysis System (WGAS) is developed to overcome limitations in analysis setup efficiency, data and procedure sharing, as well as security issues in existing commercial and public domain solutions. It also incorporates unique functions and resources for more accurate and flexible GeneChip analysis.

Availability: WGAS is freely available at: http://arrayanalysis.

SNP Function Portal: a web database for exploring the function implication of SNP alleles.

Motivation: Finding the potential functional significance of SNPs is a major bottleneck in understanding genome-wide SNP scanning results, as the related functional data are distributed across many different databases. The SNP Function Portal is designed to be a clearing house for all public domain SNP functional annotation data, as well as in-house functional annotations derived from different data sources. It currently contains SNP functional annotations in six major categories including genomic elements, transcription regulation, protein function, pathway, disease and population genetics.

Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data.

Genome-wide expression profiling is a powerful tool for implicating novel gene ensembles in cellular mechanisms of health and disease. The most popular platform for genome-wide expression profiling is the Affymetrix GeneChip. However, its selection of probes relied on earlier genome and transcriptome annotation which is significantly different from current knowledge.