Identifying Causal Genes and Dysregulated Pathways in Complex Diseases

In complex diseases, various combinations of genomic perturbations often lead to the same phenotype. On a molecular level, combinations of genomic perturbations are assumed to dys-regulate the same cellular pathways. Such a pathway-centric perspective is fundamental to understanding the mechanisms of complex diseases and the identification of potential drug targets. In order to provide an integrated perspective on complex disease mechanisms, we developed a novel computational method to simultaneously identify causal genes and dys-regulated pathways. First, we identified a representative set of genes that are differentially expressed in cancer compared to non-tumor control cases. Assuming that disease-associated gene expression changes are caused by genomic alterations, we determined potential paths from such genomic causes to target genes through a network of molecular interactions. Applying our method to sets of genomic alterations and gene expression profiles of 158 Glioblastoma multiforme (GBM) patients we uncovered candidate causal genes and causal paths that are potentially responsible for the altered expression of disease genes. We discovered a set of putative causal genes that potentially play a role in the disease. Combining an expression Quantitative Trait Loci (eQTL) analysis with pathway information, our approach allowed us not only to identify potential causal genes but also to find intermediate nodes and pathways mediating the information flow between causal and target genes. Our results indicate that different genomic perturbations indeed dys-regulate the same functional pathways, supporting a pathway-centric perspective of cancer. While copy number alterations and gene expression data of glioblastoma patients provided opportunities to test our approach, our method can be applied to any disease system where genetic variations play a fundamental causal role

A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individual

Genomic prediction for growth using a low-density SNP panel in dromedary camels

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees

Genomic prediction for growth using a low-density SNP panel in dromedary camels

For thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value \u3c 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees

Mining the Drosophila gustatory receptor family for new thermosensitive proteins : basic science and tool development

Extrinsic control of neural activity is a powerful paradigm for understanding how neural circuits operate and regulate behavior. Traditionally, optogenetic tools are used to activate or inhibit neuronal activity with light. However, using visible light as the stimulus has some limitations, such as limited penetration in opaque tissue and overlap of absorption spectra when using multiple probes. A complementary approach is to use temperature as a stimulus, and thermosensitive TRP channels as the thermogenetic probes. These channels also have some limitations, particularly in their temperature sensitivity range. A new and exciting candidate for developing new thermogenetic tools has been recently identified as Gr28bD, a member of the Drosophila gustatory receptor family, normally involved in high-temperature avoidance behavior. My work on Gr28bD started with a characterization of its biophysical properties, particularly temperature sensitivity and ionic selectivity (Chapter 1). Then, to expand the pool of potential candidates for thermogenetic tools, I examined the orthologs of Gr28bD in other species of Drosophila, and I found five other receptors that have distinct thermosensitive properties (Chapter 2). To better understand the mechanism of thermosensitivity, our team successfully modeled the molecular structure of Gr28bD, obtaining preliminary evidence of its homotetrameric organization. To obtain further information on the structural and functional elements of this channel, I tested a series of Gr28bD mutants (Chapter 3). Finally, I participated in writing a book chapter on new computational methods for testing ion channel kinetic mechanisms (Chapter 4).Includes bibliographical references

PROGRAM, THE NEBRASKA ACADEMY OF SCIENCES: One Hundred-Thirty-First Annual Meeting, APRIL 23-24, 2021. ONLINE

AFFILIATED SOCIETIES OF THE NEBRASKA ACADEMY OF SCIENCES, INC. 1.American Association of Physics Teachers, Nebraska Section: Web site: http://www.aapt.org/sections/officers.cfm?section=Nebraska 2.Friends of Loren Eiseley: Web site: http://www.eiseley.org/ 3.Lincoln Gem & Mineral Club: Web site: http://www.lincolngemmineralclub.org/ 4.Nebraska Chapter, National Council for Geographic Education 5.Nebraska Geological Society: Web site: http://www.nebraskageologicalsociety.org Sponsors of a $50 award to the outstanding student paper presented at the Nebraska Academy of SciencesAnnual Meeting, Earth Science /Nebraska Chapter, National Council Sections 6.Nebraska Graduate Women in Science 7.Nebraska Junior Academy of Sciences: Web site: http://www.nebraskajunioracademyofsciences.org/ 8.Nebraska Ornithologists’ Union: Web site: http://www.noubirds.org/ 9.Nebraska Psychological Association: http://www.nebpsych.org/ 10.Nebraska-Southeast South Dakota Section Mathematical Association of America: Web site: http://sections.maa.org/nesesd/ 11.Nebraska Space Grant Consortium: Web site: http://www.ne.spacegrant.org/ CONTENTS AERONAUTICS & SPACE SCIENCE ANTHROPOLOGY APPLIED SCIENCE & TECHNOLOGY BIOLOGICAL & MEDICAL SCIENCES COLLEGIATE ACADEMY: BIOLOGY COLLEGIATE ACADEMY: CHEMISTRY & PHYSICS EARTH SCIENCES ENVIRONMENTAL SCIENCES GENERAL CHEMISTRY GENERAL PHYSICS TEACHING OF SCIENCE & MATHEMATICS 2020-2021 PROGRAM COMMITTEE 2020-2021 EXECUTIVE COMMITTEE FRIENDS OF THE ACADEMY NEBRASKA ACADEMY OF SCIENCS FRIEND OF SCIENCE AWARD WINNERS FRIEND OF SCIENCE AWARD TO DR PAUL KAR

A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample

Evolution of Animal Microbial Communities in Response to Environmental Stress

info:eu-repo/semantics/publishedVersio

Доповнена реальність в освіті

This volume represents the proceedings of the 1st International Workshop on Augmented Reality in Education (AREdu 2018), held in Kryvyi Rih, Ukraine, in October 2, 2018. It comprises 24 contributed papers that were carefully peer-reviewed and selected from 41 submissions. The accepted papers present the state-of-the-art overview of successful cases and provides guidelines for future research.Цей том репрезентує матеріали 1-го Міжнародного семінару "Доповнена реальність в освіті" (AREdu 2018), що відбувя 2 жовтня 2018 року в м. Кривий Ріг, Україна. До нього входять 24 статті, які були ретельно переглянуті та обрані з 41 подання. У прийнятих роботах представлений найсучасніший огляд успішних випадків та окреслено напрями майбутніх досліджень

Cross-Species Genome-Wide Analysis Reveals Molecular and Functional Diversity of the Unconventional Interferon-ω Subtype

Innate immune interferons (IFNs), particularly type I IFNs, are primary mediators regulating animal antiviral, antitumor, and cell-proliferative activity. These antiviral cytokines have evolved remarkable molecular and functional diversity to confront ever-evolving viral threats and physiological regulation. We have annotated IFN gene families across 110 animal genomes, and showed that IFN genes, after originating in jawed fishes, had several significant evolutionary surges in vertebrate species of amphibians, bats and ungulates, particularly pigs and cattle. For example, pigs have the largest but still expanding type I IFN family consisting of nearly 60 IFN-coding genes that encode seven IFN subtypes including multigene subtypes of IFN-α, -δ, and -ω. Whereas, subtypes such as IFN-α and -β have been widely studied in many species, the unconventional subtypes such as IFN-ω have barely been investigated. We have cross-species defined the IFN evolution, and shown that unconventional IFN subtypes particularly the IFN-ω subtype have evolved several novel features including: (1) being a signature multi-gene subtype expanding primarily in mammals such as bats and ungulates, (2) emerging isoforms that have superior antiviral potency than typical IFN-α, (3) highly cross-species antiviral (but little anti-proliferative) activity exerted in cells of humans and other mammalian species, and (4) demonstrating potential novel molecular and functional properties. This study focused on IFN-ω to investigate the immunogenetic evolution and functional diversity of unconventional IFN subtypes, which may further IFN-based novel antiviral design pertinent to their cross-species high antiviral and novel activities