A Neuronal Identity Code for the Odorant Receptor-Specific
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PARSANA-DISSERTATION-2020.Pdf
DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks. -
Sex-Specific Hippocampal 5-Hydroxymethylcytosine Is Disrupted in Response to Acute Stress Ligia A
University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Faculty Publications, Department of Statistics Statistics, Department of 2016 Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress Ligia A. Papale University of Wisconsin, [email protected] Sisi Li University of Wisconsin, [email protected] Andy Madrid University of Wisconsin, [email protected] Qi Zhang University of Nebraska-Lincoln, [email protected] Li Chen Emory University See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/statisticsfacpub Part of the Other Statistics and Probability Commons Papale, Ligia A.; Li, Sisi; Madrid, Andy; Zhang, Qi; Chen, Li; Chopra, Pankaj; Jin, Peng; Keles, Sunduz; and Alisch, Reid S., "Sex- specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress" (2016). Faculty Publications, Department of Statistics. 62. https://digitalcommons.unl.edu/statisticsfacpub/62 This Article is brought to you for free and open access by the Statistics, Department of at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Faculty Publications, Department of Statistics by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Ligia A. Papale, Sisi Li, Andy Madrid, Qi Zhang, Li Chen, Pankaj Chopra, Peng Jin, Sunduz Keles, and Reid S. Alisch This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/statisticsfacpub/62 Neurobiology of Disease 96 (2016) 54–66 Contents lists available at ScienceDirect Neurobiology of Disease journal homepage: www.elsevier.com/locate/ynbdi Sex-specific hippocampal 5-hydroxymethylcytosine is disrupted in response to acute stress Ligia A. Papale a,1,SisiLia,c,1, Andy Madrid a,c,QiZhangd,LiChene,PankajChoprae,PengJine, Sündüz Keleş b, Reid S. -
Genome-Wide Association Study to Identify Genomic Regions And
www.nature.com/scientificreports OPEN Genome‑wide association study to identify genomic regions and positional candidate genes associated with male fertility in beef cattle H. Sweett1, P. A. S. Fonseca1, A. Suárez‑Vega1, A. Livernois1,2, F. Miglior1 & A. Cánovas1* Fertility plays a key role in the success of calf production, but there is evidence that reproductive efciency in beef cattle has decreased during the past half‑century worldwide. Therefore, identifying animals with superior fertility could signifcantly impact cow‑calf production efciency. The objective of this research was to identify candidate regions afecting bull fertility in beef cattle and positional candidate genes annotated within these regions. A GWAS using a weighted single‑step genomic BLUP approach was performed on 265 crossbred beef bulls to identify markers associated with scrotal circumference (SC) and sperm motility (SM). Eight windows containing 32 positional candidate genes and fve windows containing 28 positional candidate genes explained more than 1% of the genetic variance for SC and SM, respectively. These windows were selected to perform gene annotation, QTL enrichment, and functional analyses. Functional candidate gene prioritization analysis revealed 14 prioritized candidate genes for SC of which MAP3K1 and VIP were previously found to play roles in male fertility. A diferent set of 14 prioritized genes were identifed for SM and fve were previously identifed as regulators of male fertility (SOD2, TCP1, PACRG, SPEF2, PRLR). Signifcant enrichment results were identifed for fertility and body conformation QTLs within the candidate windows. Gene ontology enrichment analysis including biological processes, molecular functions, and cellular components revealed signifcant GO terms associated with male fertility. -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like, -
Identification of Novel Kirrel3 Gene Splice Variants in Adult Human
Durcan et al. BMC Physiology 2014, 14:11 http://www.biomedcentral.com/1472-6793/14/11 RESEARCH ARTICLE Open Access Identification of novel Kirrel3 gene splice variants in adult human skeletal muscle Peter Joseph Durcan1, Johannes D Conradie1, Mari Van deVyver2 and Kathryn Helen Myburgh1* Abstract Background: Multiple cell types including trophoblasts, osteoclasts and myoblasts require somatic cell fusion events as part of their physiological functions. In Drosophila Melanogaster the paralogus type 1 transmembrane receptors and members of the immunoglobulin superfamily Kin of Irre (Kirre) and roughest (Rst) regulate myoblast fusion during embryonic development. Present within the human genome are three homologs to Kirre termed Kin of Irre like (Kirrel) 1, 2 and 3. Currently it is unknown if Kirrel3 is expressed in adult human skeletal muscle. Results: We investigated (using PCR and Western blot) Kirrel3 in adult human skeletal muscle samples taken at rest and after mild exercise induced muscle damage. Kirrel3 mRNA expression was verified by sequencing and protein presence via blotting with 2 different anti-Kirrel3 protein antibodies. Evidence for three alternatively spliced Kirrel3 mRNA transcripts in adult human skeletal muscle was obtained. Kirrel3 mRNA in adult human skeletal muscle was detected at low or moderate levels, or not at all. This sporadic expression suggests that Kirrel3 is expressed in a pulsatile manner. Several anti Kirrel3 immunoreactive proteins were detected in all adult human skeletal muscle samples analysed and results suggest the presence of different isoforms or posttranslational modification, or both. Conclusion: The results presented here demonstrate for the first time that there are at least 3 splice variants of Kirrel3 expressed in adult human skeletal muscle, two of which have never previously been identified in human muscle. -
KIRREL Is Differentially Expressed in Adipose Tissue From
KIRREL is differentially expressed in adipose tissue from “fertil+” and “fertil-” cows: in vitro role in ovary? Stéphanie Coyral-Castel, Christelle Ramé, Juliette Cognie, Jerôme Lecardonnel, Sylvain Marthey, Diane Esquerré, Christelle Hennequet-Antier, Sébastien Elis, Sébastien Fritz, Mekki Boussaha, et al. To cite this version: Stéphanie Coyral-Castel, Christelle Ramé, Juliette Cognie, Jerôme Lecardonnel, Sylvain Marthey, et al.. KIRREL is differentially expressed in adipose tissue from “fertil+” and “fertil-” cows: invitro role in ovary?. Reproduction -Cambridge- Supplement-, Society for Reproduction and Fertility, 2018, 155 (2), pp.181-196. 10.1530/REP-17-0649. hal-02625059 HAL Id: hal-02625059 https://hal.inrae.fr/hal-02625059 Submitted on 26 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Copyright Page 1 of 49Reproduction Advance Publication first posted on 23 November 2017 as Manuscript REP-17-0649 1 KIRREL is differentially expressed in adipose tissue from “fertil+” and “fertil-” cows: 2 in vitro role in ovary? 3 4 S Coyral-Castel1,2,3,4,5, -
Identification of Candidate Genes and Pathways Associated with Obesity
animals Article Identification of Candidate Genes and Pathways Associated with Obesity-Related Traits in Canines via Gene-Set Enrichment and Pathway-Based GWAS Analysis Sunirmal Sheet y, Srikanth Krishnamoorthy y , Jihye Cha, Soyoung Choi and Bong-Hwan Choi * Animal Genome & Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, Korea; [email protected] (S.S.); [email protected] (S.K.); [email protected] (J.C.); [email protected] (S.C.) * Correspondence: [email protected]; Tel.: +82-10-8143-5164 These authors contributed equally. y Received: 10 October 2020; Accepted: 6 November 2020; Published: 9 November 2020 Simple Summary: Obesity is a serious health issue and is increasing at an alarming rate in several dog breeds, but there is limited information on the genetic mechanism underlying it. Moreover, there have been very few reports on genetic markers associated with canine obesity. These studies were limited to the use of a single breed in the association study. In this study, we have performed a GWAS and supplemented it with gene-set enrichment and pathway-based analyses to identify causative loci and genes associated with canine obesity in 18 different dog breeds. From the GWAS, the significant markers associated with obesity-related traits including body weight (CACNA1B, C22orf39, U6, MYH14, PTPN2, SEH1L) and blood sugar (PRSS55, GRIK2), were identified. Furthermore, the gene-set enrichment and pathway-based analysis (GESA) highlighted five enriched pathways (Wnt signaling pathway, adherens junction, pathways in cancer, axon guidance, and insulin secretion) and seven GO terms (fat cell differentiation, calcium ion binding, cytoplasm, nucleus, phospholipid transport, central nervous system development, and cell surface) which were found to be shared among all the traits. -
Whole Exome Sequencing in Families at High Risk for Hodgkin Lymphoma: Identification of a Predisposing Mutation in the KDR Gene
Hodgkin Lymphoma SUPPLEMENTARY APPENDIX Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 1Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 2Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; 3Ad - vanced Biomedical Computing Center, Leidos Biomedical Research Inc.; Frederick National Laboratory for Cancer Research, Frederick, MD; 4Westat, Inc., Rockville MD; 5Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD; and 6Human Genetics Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA ©2016 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2015.135475 Received: August 19, 2015. Accepted: January 7, 2016. Pre-published: June 13, 2016. Correspondence: [email protected] Supplemental Author Information: NCI DCEG Cancer Sequencing Working Group: Mark H. Greene, Allan Hildesheim, Nan Hu, Maria Theresa Landi, Jennifer Loud, Phuong Mai, Lisa Mirabello, Lindsay Morton, Dilys Parry, Anand Pathak, Douglas R. Stewart, Philip R. Taylor, Geoffrey S. Tobias, Xiaohong R. Yang, Guoqin Yu NCI DCEG Cancer Genomics Research Laboratory: Salma Chowdhury, Michael Cullen, Casey Dagnall, Herbert Higson, Amy A. -
Family of Neural Wiring Receptors in Bilaterians Defined by Phylogenetic, Biochemical, and Structural Evidence
Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence Shouqiang Chenga,1, Yeonwoo Parkb,1, Justyna D. Kurletoa,c,1, Mili Jeond, Kai Zinnd, Joseph W. Thorntonb,e,f, and Engin Özkana,2 aDepartment of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637; bCommittee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL 60637; cFaculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland; dDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125; eDepartment of Human Genetics, The University of Chicago, Chicago, IL 60637; and fDepartment of Ecology and Evolution, The University of Chicago, Chicago, IL 60637 Edited by Rachelle Gaudet, Harvard University, Cambridge, MA, and accepted by Editorial Board Member Jeremy Nathans April 8, 2019 (received for review November 5, 2018) The evolution of complex nervous systems was accompanied by the Most of the Dprs and DIPs that have been studied thus far are expansion of numerous protein families, including cell-adhesion expressed exclusively in the nervous system. In the pupal optic molecules, surface receptors, and their ligands. These proteins lobe, the larval ventral nerve cord, olfactory receptor neurons, and mediate axonal guidance, synapse targeting, and other neuronal the neuromuscular system, each Dpr and DIP is expressed in a wiring-related functions. Recently, 32 interacting cell surface pro- unique subset of neurons (5, 7–9). One Dpr is also expressed in teins belonging to two newly defined families of the Ig superfamily postsynaptic muscle cells (10). In the optic lobe, Dprs and DIPs (IgSF) in fruit flies were discovered to label different subsets of are expressed in distinctive combinations in different neuronal neurons in the brain and ventral nerve cord. -
Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in -
In Silico Approach to Calculate the Transcript Capacity
In silico approach to calculate the transcript capacity Young-Sup Lee, Kyung-Hye Won, Jae-Don Oh*, Donghyun Shin** Department of Animal Biotechnology, Chonbuk National University, Jeonju 54896, Korea Original article We sought the novel concept, transcript capacity (TC) and analyzed TC. Our approach to estimate TC was through an in silico method. TC refers to the capacity that a transcript ex- eISSN 2234-0742 erts in a cell as enzyme or protein function after translation. We used the genome-wide Genomics Inform 2019;17(3):e31 association study (GWAS) beta effect and transcription level in RNA-sequencing to esti- https://doi.org/10.5808/GI.2019.17.3.e31 mate TC. The trait was body fat percent and the transcript reads were obtained from the human protein atlas. The assumption was that the GWAS beta effect is the gene’s effect and TC was related to the corresponding gene effect and transcript reads. Further, we sur- Received: September 2, 2019 veyed gene ontology (GO) in the highest TC and the lowest TC genes. The most frequent Revised: September 18, 2019 GOs with the highest TC were neuronal-related and cell projection organization related. Accepted: September 19, 2019 The most frequent GOs with the lowest TC were wound-healing related and embryo devel- opment related. We expect that our analysis contributes to estimating TC in the diverse *Corresponding author: E-mail: [email protected] species and playing a benevolent role to the new bioinformatic analysis. **Corresponding author: Keywords: fat, genome-wide association study, in silico method, transcript capacity, RNA- E-mail: [email protected] seq Introduction There have been various experimental studies regarding enzyme activity [1,2]. -
Human KIRREL / NEPH1 / KIRREL1 Protein (Fc Tag)
Human KIRREL / NEPH1 / KIRREL1 Protein (Fc Tag) Catalog Number: 15752-H02H General Information SDS-PAGE: Gene Name Synonym: NEPH1 Protein Construction: A DNA sequence encoding the human KIRREL (NP_060710.3) (Met1-Leu493) was expressed with the Fc region of human IgG1 at the C-terminus. Source: Human Expression Host: HEK293 Cells QC Testing Purity: > 95 % as determined by SDS-PAGE Endotoxin: Protein Description < 1.0 EU per μg of the protein as determined by the LAL method NEPH1 (KIRREL1) belongs to a family of three closely related Stability: transmembrane proteins of the Ig superfamily with a structure similar to that of nephrin. All three Neph proteins share a conserved podocin-binding ℃ Samples are stable for up to twelve months from date of receipt at -70 motif; mutation of a centrally located tyrosine residue dramatically lowers the affinity of Neph1 for podocin. Neph1 triggers AP-1 activation similarly to Gln 17 Predicted N terminal: nephrin but requires the presence of Tec family kinases for efficient Molecular Mass: transactivation. Neph1 consists of a signal peptide, five Ig-like C2-type domains with the middle domain overlapping with a PKD-like domain, an The recombinant human KIRREL/Fc comprises 715 amino acids and has a RGD sequence, a transmembrane domain and a cytoplasmic tail, which is predicted molecular mass of 78.8 kDa. The apparent molecular mass of the expressed in slit diaphragm domains of podocytes and in vertebrate and protein is approximately 96.1 kDa in SDS-PAGE under reducing conditions. invertebrate nervous systems. Neph1 is abundantly expressed in the kidney, specifically expressed in podocytes of kidney glomeruli, and plays a Formulation: significant role in the normal development and function of the glomerular permeability.