Content-rich biological network constructed by mining PubMed abstracts

BACKGROUND: The integration of the rapidly expanding corpus of information about the genome, transcriptome, and proteome, engendered by powerful technological advances, such as microarrays, and the availability of genomic sequence from multiple species, challenges the grasp and comprehension of the scientific community. Despite the existence of text-mining methods that identify biological relationships based on the textual co-occurrence of gene/protein terms or similarities in abstract texts, knowledge of the underlying molecular connections on a large scale, which is prerequisite to understanding novel biological processes, lags far behind the accumulation of data. While computationally efficient, the co-occurrence-based approaches fail to characterize (e.g., inhibition or stimulation, directionality) biological interactions. Programs with natural language processing (NLP) capability have been created to address these limitations, however, they are in general not readily accessible to the public. RESULTS: We present a NLP-based text-mining approach, Chilibot, which constructs content-rich relationship networks among biological concepts, genes, proteins, or drugs. Amongst its features, suggestions for new hypotheses can be generated. Lastly, we provide evidence that the connectivity of molecular networks extracted from the biological literature follows the power-law distribution, indicating scale-free topologies consistent with the results of previous experimental analyses. CONCLUSIONS: Chilibot distills scientific relationships from knowledge available throughout a wide range of biological domains and presents these in a content-rich graphical format, thus integrating general biomedical knowledge with the specialized knowledge and interests of the user. Chilibot can be accessed free of charge to academic users

Oliz, a suite of Perl scripts that assist in the design of microarrays using 50mer oligonucleotides from the 3' untranslated region

BACKGROUND: Identifying reliable oligonucleotide sequences for use in microarray experiments is a complex process. Two key issues are the accuracy of the input sequences and the specificity of the oligonucleotide sequences. RESULTS: We provide a suite of Perl scripts that facilitates the search for gene-specific oligonucleotides for microarray experiments. Genes of interest are first identified in the form of UniGene clusters. The sequences of these clusters were extracted and assembled into contigs to increase their accuracy. The 3' untranslated region (3'UTR) of the contig was parsed. Then, multiple 50mer oligonucleotide sequences with similar melting temperature were obtained from each 3'UTR. These sequences were analyzed for gene specificity. Five Cy3-labeled cDNAs were used to empirically verify the specificity of a set of 1814 50mers. CONCLUSION: Oliz can be used to select oligonucleotide sequences for microarrays. Oliz is freely available for academic users at http://www.utmem.edu/pharmacology/otherlinks/oliz.htm

Local ␣-Bungarotoxin-Sensitive Nicotinic Receptors Modulate Hippocampal Norepinephrine Release by Systemic Nicotine 1

ABSTRACT Previous studies have shown that nicotinic receptors (NAChRs) accessible from the cerebral aqueduct of the brainstem mediate the hippocampal norepinephrine (NE) release induced by i.v. nicotine. The present study was designed to investigate the role of hippocampal NAChRs in this process. Nicotinic antagonists were microinjected or microdialyzed into the hippocampus (HP) before administering nicotine (0.09 mg/kg over 60 s, i.v.) to freely moving rats. ␣-Bungarotoxin (0.3 nmol by microinjection) blocked nicotine-induced hippocampal NE release by 47% (p Ͻ .05) and abolished the effect of 0.065 mg/kg nicotine. Methyllycaconitine (1.4 -5.6 mM in the dialysate) inhibited the stimulatory effect of nicotine 0.09 mg/kg by 48 to 75% (p Ͻ .05). In contrast, mecamylamine (2.9 -5.8 mM) and dihydro-␤-erythroidine (7-14 mM) were completely ineffective. The role of hippocampal NAChRs was demonstrated further by selectively desensitizing these receptors before the systemic infusion of nicotine. To do so, the HP was pretreated with nicotine (0.1 mM) delivered through the microdialysis probe; this concentration was calculated to yield tissue concentrations similar to those produced by the systemic infusions of nicotine. Dialyzing this concentration of nicotine into the HP inhibited the NE response to i.v. nicotine by 34% (p Ͻ .05), and 1.0 mM nicotine reduced the response by 40%. These studies indicate that ␣-bungarotoxin-sensitive hippocampal NAChRs, probably containing ␣7 subunits, modulate hippocampal NE release because of systemic nicotine

Genome-Wide Gene Expression Profiling of Nucleus Accumbens Neurons Projecting to Ventral Pallidum Using both Microarray and Transcriptome Sequencing

The cellular heterogeneity of brain poses a particularly thorny issue in genome-wide gene expression studies. Because laser capture microdissection (LCM) enables the precise extraction of a small area of tissue, we combined LCM with neuronal track tracing to collect nucleus accumbens shell neurons that project to ventral pallidum, which are of particular interest in the study of reward and addiction. Four independent biological samples of accumbens projection neurons were obtained. Approximately 500 pg of total RNA from each sample was then amplified linearly and subjected to Affymetrix microarray and Applied Biosystems sequencing by oligonucleotide ligation and detection (SOLiD) transcriptome sequencing (RNA-seq). A total of 375 million 50-bp reads were obtained from RNA-seq. Approximately 57% of these reads were mapped to the rat reference genome (Baylor 3.4/rn4). Approximately 11,000 unique RefSeq genes and 100,000 unique exons were identified from each sample. Of the unmapped reads, the quality scores were 4.74 ± 0.42 lower than the mapped reads. When RNA-seq and microarray data from the same samples were compared, Pearson correlations were between 0.764 and 0.798. The variances in data obtained for the four samples by microarray and RNA-seq were similar for medium to high abundance genes, but less among low abundance genes detected by microarray. Analysis of 34 genes by real-time polymerase chain reaction showed higher correlation with RNA-seq (0.66) than with microarray (0.46). Further analysis showed 20–30 million 50-bp reads are sufficient to provide estimates of gene expression levels comparable to those produced by microarray. In summary, this study showed that picogram quantities of total RNA obtained by LCM of ∼700 individual neurons is sufficient to take advantage of the benefits provided by the transcriptome sequencing technology, such as low background noise, high dynamic range, and high precision

SPECT imaging of Moyamoya disease using 99mTc-HM-PAO comparison with computed tomography findings

99mTc-HM-PAO was used to evaluate regional cerebral blood flow in a 26-year-old woman with Moyamoya disease. This patient had an 18-month history of recurrent neurologic deficits and had angiographic evidence of Moyamoya disease. She had used oral contraceptives and cigarettes, but had no other risk factors for stroke. Single photon emission computed tomographic images showed bilateral and asymmetric reductions in blood flow to anterior and lateral brain regions. These findings correlated better with clinical symptomatology and suggested more extensive brain involvement than did computed tomography.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27118/1/0000110.pd

A Revamped Rat Reference Genome Improves the Discovery of Genetic Diversity in Laboratory Rats

The seventh iteration of the reference genome assembly for Rattus norvegicus-mRatBN7.2-corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared with its predecessor. Gene annotations are now more complete, improving the mapping precision of genomic, transcriptomic, and proteomics datasets. We jointly analyzed 163 short-read whole-genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined ∼20.0 million sequence variations, of which 18,700 are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Search for vector-like T quarks decaying to top quarks and Higgs bosons in the all-hadronic channel using jet substructure

Peer reviewe