A Web Application to Explore Human SNP-Associations and Annotate SNP-Sets
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Accurate Annotation of Human Protein-Coding Small Open Reading Frames
HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nat Chem Manuscript Author Biol. Author Manuscript Author manuscript; available in PMC 2020 June 09. Published in final edited form as: Nat Chem Biol. 2020 April ; 16(4): 458–468. doi:10.1038/s41589-019-0425-0. Accurate annotation of human protein-coding small open reading frames Thomas F. Martinez1,*, Qian Chu1, Cynthia Donaldson1, Dan Tan1, Maxim N. Shokhirev2, Alan Saghatelian1,* 1Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California 92037, USA 2Razavi Newman Integrative Genomics Bioinformatics Core, Salk Institute for Biological Studies, La Jolla, California 92037, USA Abstract Functional protein-coding small open reading frames (smORFs) are emerging as an important class of genes. However, the number of translated smORFs in the human genome is unclear because proteogenomic methods are not sensitive enough, and, as we show, Ribo-Seq strategies require additional measures to ensure comprehensive and accurate smORF annotation. Here, we integrate de novo transcriptome assembly and Ribo-Seq into an improved workflow that overcomes obstacles with previous methods to more confidently annotate thousands of smORFs. Evolutionary conservation analyses suggest that hundreds of smORF-encoded microproteins are likely functional. Additionally, many smORFs are regulated during fundamental biological processes, such as cell stress. Peptides derived from smORFs are also detectable on human leukocyte antigen complexes, revealing smORFs as a source of antigens. Thus, by including additional validation into our smORF annotation workflow, we accurately identify thousands of unannotated translated smORFs that will provide a rich pool of unexplored, functional human genes. Annotation of open reading frames (ORFs) from genome sequencing was initially carried out by locating in-frame start (AUG) and stop codons1–3. -
Whole-Genome Sequencing for Tracing the Genetic Diversity of Brucella Abortus and Brucella Melitensis Isolated from Livestock in Egypt
pathogens Article Whole-Genome Sequencing for Tracing the Genetic Diversity of Brucella abortus and Brucella melitensis Isolated from Livestock in Egypt Aman Ullah Khan 1,2,3 , Falk Melzer 1, Ashraf E. Sayour 4, Waleed S. Shell 5, Jörg Linde 1, Mostafa Abdel-Glil 1,6 , Sherif A. G. E. El-Soally 7, Mandy C. Elschner 1, Hossam E. M. Sayour 8 , Eman Shawkat Ramadan 9, Shereen Aziz Mohamed 10, Ashraf Hendam 11 , Rania I. Ismail 4, Lubna F. Farahat 10, Uwe Roesler 2, Heinrich Neubauer 1 and Hosny El-Adawy 1,12,* 1 Institute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, 07743 Jena, Germany; AmanUllah.Khan@fli.de (A.U.K.); falk.melzer@fli.de (F.M.); Joerg.Linde@fli.de (J.L.); Mostafa.AbdelGlil@fli.de (M.A.-G.); mandy.elschner@fli.de (M.C.E.); Heinrich.neubauer@fli.de (H.N.) 2 Institute for Animal Hygiene and Environmental Health, Free University of Berlin, 14163 Berlin, Germany; [email protected] 3 Department of Pathobiology, University of Veterinary and Animal Sciences (Jhang Campus), Lahore 54000, Pakistan 4 Department of Brucellosis, Animal Health Research Institute, Agricultural Research Center, Dokki, Giza 12618, Egypt; [email protected] (A.E.S.); [email protected] (R.I.I.) 5 Central Laboratory for Evaluation of Veterinary Biologics, Agricultural Research Center, Abbassia, Citation: Khan, A.U.; Melzer, F.; Cairo 11517, Egypt; [email protected] 6 Sayour, A.E.; Shell, W.S.; Linde, J.; Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Elzera’a Square, Abdel-Glil, M.; El-Soally, S.A.G.E.; Zagazig 44519, Egypt 7 Veterinary Service Department, Armed Forces Logistics Authority, Egyptian Armed Forces, Nasr City, Elschner, M.C.; Sayour, H.E.M.; Cairo 11765, Egypt; [email protected] Ramadan, E.S.; et al. -
MEPE Is a Novel Regulator of Growth Plate Cartilage Mineralization
Edinburgh Research Explorer MEPE is a novel regulator of growth plate cartilage mineralization Citation for published version: Staines, K, Mackenzie, NCW, Clarkin, CE, Zelenchuk, L, Rowe, PS, MacRae, VE & Farquharson, C 2012, 'MEPE is a novel regulator of growth plate cartilage mineralization', Bone, vol. 51, no. 3, pp. 418-430. https://doi.org/10.1016/j.bone.2012.06.022 Digital Object Identifier (DOI): 10.1016/j.bone.2012.06.022 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Bone Publisher Rights Statement: Available under Open Access General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 01. Oct. 2021 Bone 51 (2012) 418–430 Contents lists available at SciVerse ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Original Full Length Article MEPE is a novel regulator of growth plate cartilage mineralization K.A. Staines a,⁎, N.C.W. Mackenzie a, C.E. Clarkin b, L. Zelenchuk c, P.S. Rowe c, V.E. -
CERENKOV: Computational Elucidation of the Regulatory Noncoding Variome
CERENKOV: Computational Elucidation of the Regulatory Noncoding Variome Yao Yao∗ Zheng Liu∗ Satpreet Singh Oregon State University Oregon State University Oregon State University EECS EECS EECS [email protected] [email protected] [email protected] Qi Wei Stephen A. Ramsey Oregon State University Oregon State University EECS Department of Biomedical Sciences [email protected] Corvallis, Oregon 97330 [email protected] ABSTRACT (hAVGRANKi = 3.877). The source code for CERENKOV We describe a novel computational approach, CERENKOV is available on GitHub and the SNP feature data files are (Computational Elucidation of the REgulatory NonKOd- available for download via the CERENKOV website. ing Variome), for discriminating regulatory single nucleotide polymorphisms (rSNPs) from non-regulatory SNPs within CCS CONCEPTS noncoding genetic loci. CERENKOV is specifically designed • Computing methodologies → Machine learning; • for recognizing rSNPs in the context of a post-analysis of a Applied computing → Computational biology; Bioin- genome-wide association study (GWAS); it includes a novel formatics; accuracy scoring metric (which we call average rank, or AV- GRANK) and a novel cross-validation strategy (locus-based KEYWORDS sampling) that both correctly account for the \sparse positive SNP, GWAS, noncoding, rSNP, SNV, machine learning bag" nature of the GWAS post-analysis rSNP recognition problem. We trained and validated CERENKOV using a reference set of 15,331 SNPs (the OSU17 SNP set) whose composition is based -
MODBASE: a Database of Annotated Comparative Protein Structure Models and Associated Resources Ursula Pieper1,2, Narayanan Eswar1,2, Fred P
Nucleic Acids Research, 2006, Vol. 34, Database issue D291–D295 doi:10.1093/nar/gkj059 MODBASE: a database of annotated comparative protein structure models and associated resources Ursula Pieper1,2, Narayanan Eswar1,2, Fred P. Davis1,2, Hannes Braberg1,2, M. S. Madhusudhan1,2, Andrea Rossi1,2, Marc Marti-Renom1,2, Rachel Karchin1,2, Ben M. Webb1,2, David Eramian1,2,4, Min-Yi Shen1,2, Libusha Kelly1,2,5, Francisco Melo3 and Andrej Sali1,2,* 1Department of Biopharmaceutical Sciences and 2Department Pharmaceutical Chemistry, California Institute for Quantitative Biomedical Research, QB3 at Mission Bay, Office 503B, University of California at San Francisco, 1700 4th Street, San Francisco, CA 94158, USA, 3Departamento de Gene´tica Molecular y Microbiologı´a, Facultad de Ciencias Biolo´gicas, Pontificia Universidad Cato´lica de Chile, Alameda 340, Santiago, Chile, 4Graduate Group in Biophysics and 5Graduate Group in Biological and Medical Informatics, University of California, San Francisco, CA, USA Received September 14, 2005; Accepted October 5, 2005 ABSTRACT sites, interactions between yeast proteins, and func- MODBASE (http://salilab.org/modbase) is a database tional consequences of human nsSNPs (LS-SNP, of annotated comparative protein structure models http://salilab.org/LS-SNP). for all available protein sequences that can be matched to at least one known protein structure. The models are calculated by MODPIPE, an automated INTRODUCTION modeling pipeline that relies on MODELLER for fold The genome sequencing efforts are providing us with com- assignment, sequence–structure alignment, model plete genetic blueprints for hundreds of organisms, including building and model assessment (http:/salilab.org/ humans. We are now faced with the challenge of assigning, modeller). -
Genome-Wide Screen of Otosclerosis in Population Biobanks
medRxiv preprint doi: https://doi.org/10.1101/2020.11.15.20227868; this version posted November 16, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . 1 Genome-wide Screen of Otosclerosis in 2 Population Biobanks: 18 Loci and Shared 3 Heritability with Skeletal Structure 4 Joel T. Rämö1, Tuomo Kiiskinen1, Juha Karjalainen1,2,3,4, Kristi Krebs5, Mitja Kurki1,2,3,4, Aki S. 5 Havulinna6, Eija Hämäläinen1, Paavo Häppölä1, Heidi Hautakangas1, FinnGen, Konrad J. 6 Karczewski1,2,3,4, Masahiro Kanai1,2,3,4, Reedik Mägi5, Priit Palta1,5, Tõnu Esko5, Andres Metspalu5, 7 Matti Pirinen1,7,8, Samuli Ripatti1,2,7, Lili Milani5, Antti Mäkitie9, Mark J. Daly1,2,3,4,10, and Aarno 8 Palotie1,2,3,4 9 1. Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of 10 Helsinki, Helsinki, Finland 11 2. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, 12 Massachusetts, USA 13 3. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, 14 USA 15 4. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA 16 5. Estonian Genome Center, University of Tartu, Tartu, Estonia, Institute of Molecular and Cell Biology, 17 University of Tartu, Tartu, Estonia 18 6. Finnish Institute for Health and Welfare, Helsinki, Finland 19 7. Department of Public Health, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland 20 8. -
Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights Into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle
animals Article Integrating Single-Step GWAS and Bipartite Networks Reconstruction Provides Novel Insights into Yearling Weight and Carcass Traits in Hanwoo Beef Cattle Masoumeh Naserkheil 1 , Abolfazl Bahrami 1 , Deukhwan Lee 2,* and Hossein Mehrban 3 1 Department of Animal Science, University College of Agriculture and Natural Resources, University of Tehran, Karaj 77871-31587, Iran; [email protected] (M.N.); [email protected] (A.B.) 2 Department of Animal Life and Environment Sciences, Hankyong National University, Jungang-ro 327, Anseong-si, Gyeonggi-do 17579, Korea 3 Department of Animal Science, Shahrekord University, Shahrekord 88186-34141, Iran; [email protected] * Correspondence: [email protected]; Tel.: +82-31-670-5091 Received: 25 August 2020; Accepted: 6 October 2020; Published: 9 October 2020 Simple Summary: Hanwoo is an indigenous cattle breed in Korea and popular for meat production owing to its rapid growth and high-quality meat. Its yearling weight and carcass traits (backfat thickness, carcass weight, eye muscle area, and marbling score) are economically important for the selection of young and proven bulls. In recent decades, the advent of high throughput genotyping technologies has made it possible to perform genome-wide association studies (GWAS) for the detection of genomic regions associated with traits of economic interest in different species. In this study, we conducted a weighted single-step genome-wide association study which combines all genotypes, phenotypes and pedigree data in one step (ssGBLUP). It allows for the use of all SNPs simultaneously along with all phenotypes from genotyped and ungenotyped animals. Our results revealed 33 relevant genomic regions related to the traits of interest. -
Gene Expression Profiling of Corpus Luteum Reveals the Importance Of
bioRxiv preprint doi: https://doi.org/10.1101/673558; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Gene expression profiling of corpus luteum reveals the 2 importance of immune system during early pregnancy in 3 domestic sheep. 4 Kisun Pokharel1, Jaana Peippo2 Melak Weldenegodguad1, Mervi Honkatukia2, Meng-Hua Li3*, Juha 5 Kantanen1* 6 1 Natural Resources Institute Finland (Luke), Jokioinen, Finland 7 2 Nordgen – The Nordic Genetic Resources Center, Ås, Norway 8 3 College of Animal Science and Technology, China Agriculture University, Beijing, China 9 * Correspondence: MHL, [email protected]; JK, [email protected] 10 Abstract: The majority of pregnancy loss in ruminants occurs during the preimplantation stage, which is thus 11 the most critical period determining reproductive success. While ovulation rate is the major determinant of 12 litter size in sheep, interactions among the conceptus, corpus luteum and endometrium are essential for 13 pregnancy success. Here, we performed a comparative transcriptome study by sequencing total mRNA from 14 corpus luteum (CL) collected during the preimplantation stage of pregnancy in Finnsheep, Texel and F1 15 crosses, and mapping the RNA-Seq reads to the latest Rambouillet reference genome. A total of 21,287 genes 16 were expressed in our dataset. Highly expressed autosomal genes in the CL were associated with biological 17 processes such as progesterone formation (STAR, CYP11A1, and HSD3B1) and embryo implantation (eg. -
(From GWAS/WGS/WES) to Mechanistic Disease Insight?
How do we go from genetic discoveries (from GWAS/WGS/WES) to mechanistic disease insight? Part I – Functional annotation in risk loci 2021 Online International Statistical Genetics Workshop Danielle Posthuma | [email protected] | @dposthu | https://ctg.cncr.nl What have we learned so far? Theory underlying genetic association Setting up a genome-wide association study Quality control for genetic datasets and analysis Conducting genetic association Several post-gwas analyses including SNP h2, causal modeling, gSEM Primary outcome of a genome-wide genetic association: - Manhattan plot - Summary statistics that include an effect estimate and significance of association per variant GWAS McCarthy et al. Nat. Rev. Gent. (2008) GWAS HOW? McCarthy et al. Nat. Rev. Gent. (2008) How to gain mechanistic insight from genetic discoveries Mendelian or monogenic disorders (influenced by one mutation in one gene) • Segregation analysis (1970s – onwards) detected several genes co- segregating with disease • For each disease a mutation in one gene is sufficient to express that disease • Functional experimentation on these genes involved e.g. knock-out models to investigate that gene’s function • This has been successful for e.g. PKU, Huntington’s disease, breast cancer. • Any mechanistic insight guides treatment development How to gain mechanistic insight from genetic discoveries Polygenic disorders (influenced by 100’s of variants each of small effect) • GWAS (2006s – onwards) detected several genetic loci associated with diseases that are polygenic • For each disease a single genetic variant is not sufficient to express that disease, instead 100’s of variants cumulatively increase risk for disease • Detected loci contain 100’s of variants, sometimes no genes are implicated • Functional experimentation on these variants is not straightforward, mechanistic insight is not easily obtained for polygenic traits GWAS hits for polygenic traits often not directly useful for functional follow-up 4 issues: 1. -
Evaluation of Gene Variants in TGFB1, SERPINF1 and MEPE in a Spanish Family Affected by Otosclerosis and Tinnitus
Francisco J. Álvarez, Santiago Álvarez, Jesús Alonso, Pedro García Volumen 5 / Número 1 • http://www.revistabionatura.com RESEARCH / INVESTIGACIÓN Evaluation of Gene Variants in TGFB1, SERPINF1 and MEPE in a Spanish Family Affected by Otosclerosis and Tinnitus Francisco J. Álvarez1, Santiago Álvarez4, Jesús Alonso3, Pedro García2 DOI. 10.21931/RB/2020.05.01.7 Abstract: Otosclerosis (OTSC) is a common type of deafness affecting up to 0.4 % of Caucasians. Its familial form is inherited in an autosomal dominant fashion, although to this date, no definitive cause for OTSC has been found. In the development of OTSC, three recent genetic association studies have suggested the participation of particular point mutations and small indels in the TGFB1, SERPINF1, and MEPE genes. Consequently, replicative studies are needed to confirm the role of the proposed mutations in OTSC patients. The goal of this study was to test the presence of the candidate variants described in the genes TGFB1, 1050 SERPINF1, and MEPE in a new case of familial OTSC with seven affected individuals. DNA was extracted from saliva samples of a Spanish family with several members affected by OTSC. PCR amplified target regions of some candidate genes, and the products were purified, Sanger-sequenced, and analyzed in silico. The family subject of the study did not carry the candidate variants for OTSC described in the genes TGFB1, SERPINF1, and MEPE, although it cannot be ruled out the involvement of other mutations in genes related to their same signaling pathways. This result highlights the importance of performing replicative studies for complex diseases, such as OTCS, in families of diverse origins. -
Identification of Differentially Expressed Genes in Human Bladder Cancer Through Genome-Wide Gene Expression Profiling
521-531 24/7/06 18:28 Page 521 ONCOLOGY REPORTS 16: 521-531, 2006 521 Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling KAZUMORI KAWAKAMI1,3, HIDEKI ENOKIDA1, TOKUSHI TACHIWADA1, TAKENARI GOTANDA1, KENGO TSUNEYOSHI1, HIROYUKI KUBO1, KENRYU NISHIYAMA1, MASAKI TAKIGUCHI2, MASAYUKI NAKAGAWA1 and NAOHIKO SEKI3 1Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520; Departments of 2Biochemistry and Genetics, and 3Functional Genomics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan Received February 15, 2006; Accepted April 27, 2006 Abstract. Large-scale gene expression profiling is an effective CKS2 gene not only as a potential biomarker for diagnosing, strategy for understanding the progression of bladder cancer but also for staging human BC. This is the first report (BC). The aim of this study was to identify genes that are demonstrating that CKS2 expression is strongly correlated expressed differently in the course of BC progression and to with the progression of human BC. establish new biomarkers for BC. Specimens from 21 patients with pathologically confirmed superficial (n=10) or Introduction invasive (n=11) BC and 4 normal bladder samples were studied; samples from 14 of the 21 BC samples were subjected Bladder cancer (BC) is among the 5 most common to microarray analysis. The validity of the microarray results malignancies worldwide, and the 2nd most common tumor of was verified by real-time RT-PCR. Of the 136 up-regulated the genitourinary tract and the 2nd most common cause of genes we detected, 21 were present in all 14 BCs examined death in patients with cancer of the urinary tract (1-7). -
A Scalable Strategy for High-Throughput GFP Tagging of PNAS PLUS Endogenous Human Proteins
A scalable strategy for high-throughput GFP tagging of PNAS PLUS endogenous human proteins Manuel D. Leonettia,b,1, Sayaka Sekinec,1, Daichi Kamiyamac,2, Jonathan S. Weissmana,b,2, and Bo Huangc,2 aDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143; bHoward Hughes Medical Institute, University of California, San Francisco, CA 94143; and cDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA 94143 Contributed by Jonathan S. Weissman, April 28, 2016 (sent for review April 6, 2016; reviewed by Hazen P. Babcock and Pietro De Camilli) A central challenge of the postgenomic era is to comprehensively cost-effective manner; (ii) specificity, limiting tag insertion to the characterize the cellular role of the ∼20,000 proteins encoded in genomic target (ideally in a “scarless” manner that avoids insertion the human genome. To systematically study protein function in a of irrelevant DNA such as selection marker genes); (iii) versatility native cellular background, libraries of human cell lines expressing of the tag, preferably allowing both localization and proteomic proteins tagged with a functional sequence at their endogenous analyses; and (iv) selectability of knockin cells. Recently, a strategy loci would be very valuable. Here, using electroporation of Cas9 based on electroporation of Cas9/single-guide RNA (sgRNA) ri- nuclease/single-guide RNA ribonucleoproteins and taking advan- bonucleoprotein complexes (RNPs) has been reported that enables tage of a split-GFP system, we describe a scalable method for the both scalability and specificity (14,15).Inthisapproach,RNPsare robust, scarless, and specific tagging of endogenous human genes assembled in vitro from purified sgRNA and Cas9, both of which with GFP.