Microarray Analysis: Genome-scale hypothesis scanning

Microarrays can survey genome-wide expression patterns. Not only can these gene expression profiles be used to identify a few genes of interest, they are now being creatively applied for hypothesis generation and testin

An association-adjusted consensus deleterious scheme to classify homozygous Mis-sense mutations for personal genome interpretation

BACKGROUND: Personal genome analysis is now being considered for evaluation of disease risk in healthy individuals, utilizing both rare and common variants. Multiple scores have been developed to predict the deleteriousness of amino acid substitutions, using information on the allele frequencies, level of evolutionary conservation, and averaged structural evidence. However, agreement among these scores is limited and they likely over-estimate the fraction of the genome that is deleterious. METHOD: This study proposes an integrative approach to identify a subset of homozygous non-synonymous single nucleotide polymorphisms (nsSNPs). An 8-level classification scheme is constructed from the presence/absence of deleterious predictions combined with evidence of association with disease or complex traits. Detailed literature searches and structural validations are then performed for a subset of homozygous 826 mis-sense mutations in 575 proteins found in the genomes of 12 healthy adults. RESULTS: Implementation of the Association-Adjusted Consensus Deleterious Scheme (AACDS) classifies 11% of all predicted highly deleterious homozygous variants as most likely to influence disease risk. The number of such variants per genome ranges from 0 to 8 with no significant difference between African and Caucasian Americans. Detailed analysis of mutations affecting the APOE, MTMR2, THSB1, CHIA, αMyHC, and AMY2A proteins shows how the protein structure is likely to be disrupted, even though the associated phenotypes have not been documented in the corresponding individuals. CONCLUSIONS: The classification system for homozygous nsSNPs provides an opportunity to systematically rank nsSNPs based on suggestive evidence from annotations and sequence-based predictions. The ranking scheme, in-depth literature searches, and structural validations of highly prioritized mis-sense mutations compliment traditional sequence-based approaches and should have particular utility for the development of individualized health profiles. An online tool reporting the AACDS score for any variant is provided at the authors’ website

Cross-species comparison of genome-wide expression patterns

The rapid accumulation of microarray data from multiple species provides unprecedented opportunities to study the evolution of biological systems. Recent studies have used cross-species comparisons of expression profiles to annotate gene functions, to draw evolutionary inferences concerning specific biological processes and to study the global properties of expression networks

Genomic insights into ayurvedic and western approaches to personalized medicine

Ayurveda, an ancient Indian system of medicine documented and practised since 1500 B.C., follows a systems approach that has interesting parallels with contemporary personalized genomic medicine approaches to the understanding and management of health and disease. It is based on the trisutra, which are the three aspects of causes, features and therapeutics that are interconnected through a common organizing principle termed ‘tridosha’. Tridosha comprise three ascertainable physiological entities; vata (kinetic), pitta (metabolic) and kapha (potential) that are pervasive across systems, work in conjunction with each other, respond to the external environment and maintain homeostasis. Each individual is born with a specific proportion of tridosha that are not only genetically determined but also influenced by the environment during foetal development. Jointly they determine a person’s basic constitution, which is termed their ‘prakriti’. Development and progression of different diseases with their subtypes are thought to depend on the origin and mechanism of perturbation of the doshas, and the aim of therapeutic practice is to ensure that the doshas retain their homeostatic state. Similarly, western systems biology epitomized by translational P4 medicine envisages the integration of multiscalar genetic, cellular, physiological and environmental networks to predict phenotypic outcomes of perturbations. In this perspective article, we aim to outline the shape of a unifying scaffold that may allow the two intellectual traditions to enhance one another. Specifically, we illustrate how a unique integrative ‘Ayurgenomics’ approach can be used to integrate the trisutra concept of Ayurveda with genomics. We observe biochemical and molecular correlates of prakriti and show how these differ significantly in processes that are linked to intermediate patho-phenotypes, known to take different course in diseases. We also observe a significant enrichment of the highly connected hub genes which could explain differences in prakriti, focussing on EGLN1, a key oxygen sensor that differs between prakriti types and is linked to high altitude adaptation. Integrating our observation with the current literature, we demonstrate how EGLN1 could qualify as a molecular equivalent of tridosha that can modulate different phenotypic outcomes, where hypoxia is a cause or a consequence both during health and diseased states. Our studies affirm that integration of the trisutra framework through Ayurgenomics can guide the identification of predisposed groups of individuals and enable discovery of actionable therapeutic points in an individualized manner

Protein Modularity of Alternatively Spliced Exons Is Associated with Tissue-Specific Regulation of Alternative Splicing

Recent comparative genomic analysis of alternative splicing has shown that protein modularity is an important criterion for functional alternative splicing events. Exons that are alternatively spliced in multiple organisms are much more likely to be an exact multiple of 3 nt in length, representing a class of “modular” exons that can be inserted or removed from the transcripts without affecting the rest of the protein. To understand the precise roles of these modular exons, in this paper we have analyzed microarray data for 3,126 alternatively spliced exons across ten mouse tissues generated by Pan and coworkers. We show that modular exons are strongly associated with tissue-specific regulation of alternative splicing. Exons that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low levels show no preference for protein modularity. In contrast, alternatively spliced exons with dramatic changes of inclusion levels across mouse tissues (referred to as “tissue-switched” exons) are both strikingly biased to be modular and are strongly conserved between human and mouse. The analysis of different subsets of tissue-switched exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing

School Resource Allocation in Texas Public Schools: Study of High-Poverty, High Performing Schools and High-Poverty, Low Performing Schools

The purpose of this study was to examine the relationship between resource allocation practices in specific categorical functions and student performance in reading and math. This study utilized quantitative research methods to study the effects of spending and performance over four years of analysis. Quantitative data was acquired utilizing information from the Texas Education Agency. The data was collected from 81 campuses and represented over 1,500 students. The study's outcomes reported that little or no correlation could be found between inputs (dollars spent in three categories) and outputs (student results in reading and math). However, subgroup analysis revealed that students from non- low socioeconomic (SES) households started out higher than their low SES counterparts, and low SES students performed worse over time in both reading and math. Math results decreased more dramatically than reading indicating a need for school-level training in data analysis to ensure that limited dollars are spent appropriately. The study recommends that principals and school administrators be especially knowledgeable in critical data analysis skills. The study further recommends that state policy-makers invest more heavily in early math instruction. In addition, the current study found that student achievement, in low-SES students, especially in mathematics is very alarming. Low SES students are starting out behind the non low-SES counterparts and perform progressively worse over time. State policy makers must address these concerns

Effects of Endophyte Infection in Tall Fescue (Festuca Arundinacea: Poaceae) on Community Diversity

Recent studies have suggested that the presence of endophytes in tall fescue can lead to decreased species richness in the associated plant community. To assess the generality of this hypothesis, a field study tested the effects of endophyte infection on a 3-yr-old successional field dominated by Festuca arundinacea. The potential importance of endophyte infection relative to other environmental factors was tested by including two additional treatments: the effects of soil fertility and mowing. Contrary to previous studies, a positive relationship was found between endophyte infection frequency and diversity (N = 23, F = 5.23, R2 = 0.19, P \u3c 0.03). A strong interaction was found between the mowing treatment and endophyte infection frequency in predicting diversity (N = 22, F = 36.1, R2 = 0.84, P \u3c 0.0001), where the maximum species richness was present in plots that were both mowed and highly endophyte infected. The relationship between endophytes and diversity varied through the successional continuum (the mowing treatments) but was generally positive. The soil in mowed plots was drier than in unmowed plots (t = 2.1, df = 28, P \u3c 0.05). We suggest that heavy mowing decreases soil moisture levels enough to reduce the interspecific competitive ability of infected F. arundinacea, thereby promoting local diversity. Endophyte presence is important, but the previously reported negative relationship between endophyte infection and community diversity is probably overly simplistic in complex ecological settings

Tests for the replication of an association between Egfr and natural variation in Drosophila melanogaster wing morphology

Background Quantitative differences between individuals stem from a combination of genetic and environmental factors, with the heritable variation being shaped by evolutionary forces. Drosophila wing shape has emerged as an attractive system for genetic dissection of multi-dimensional traits. We utilize several experimental genetic methods to validation of the contribution of several polymorphisms in the Epidermal growth factor receptor (Egfr) gene to wing shape and size, that were previously mapped in populations of Drosophila melanogaster from North Carolina (NC) and California (CA). This re-evaluation utilized different genetic testcrosses to generate heterozygous individuals with a variety of genetic backgrounds as well as sampling of new alleles from Kenyan stocks. Results Only one variant, in the Egfr promoter, had replicable effects in all new experiments. However, expanded genotyping of the initial sample of inbred lines rendered the association non-significant in the CA population, while it persisted in the NC sample, suggesting population specific modification of the quantitative trait nucleotide QTN effect. Conclusion Dissection of quantitative trait variation to the nucleotide level can identify sites with replicable effects as small as one percent of the segregating genetic variation. However, the testcross approach to validate QTNs is both labor intensive and time-cThe project was funded by grants to G.G. from the David and Lucille Packard Foundation and the National Institutes of Health (R01 GM61600).Peer Reviewe

The Basic Course at U.S. Colleges and Universities: V

This paper reports the results of a survey undertaken to determine the nature of the basic course in speech as it is now taught at United States colleges and universities, and to identify important trends in instruction of the basic communication course. It appears that enrollment in the basic course is increasing. Findings are also reported concerning the orientation taken in the basic course, along with information on instructional methods used and administrative concerns connected with the basic course. The various implications of the findings are discussed