Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression
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Differences Between Human and Chimpanzee Genomes and Their Implications in Gene Expression, Protein Functions and Biochemical Properties of the Two Species Maria V
Suntsova and Buzdin BMC Genomics 2020, 21(Suppl 7):535 https://doi.org/10.1186/s12864-020-06962-8 REVIEW Open Access Differences between human and chimpanzee genomes and their implications in gene expression, protein functions and biochemical properties of the two species Maria V. Suntsova1 and Anton A. Buzdin1,2,3,4* From 11th International Young Scientists School “Systems Biology and Bioinformatics”–SBB-2019 Novosibirsk, Russia. 24-28 June 2019 Abstract Chimpanzees are the closest living relatives of humans. The divergence between human and chimpanzee ancestors dates to approximately 6,5–7,5 million years ago. Genetic features distinguishing us from chimpanzees and making us humans are still of a great interest. After divergence of their ancestor lineages, human and chimpanzee genomes underwent multiple changes including single nucleotide substitutions, deletions and duplications of DNA fragments of different size, insertion of transposable elements and chromosomal rearrangements. Human-specific single nucleotide alterations constituted 1.23% of human DNA, whereas more extended deletions and insertions cover ~ 3% of our genome. Moreover, much higher proportion is made by differential chromosomal inversions and translocations comprising several megabase-long regions or even whole chromosomes. However, despite of extensive knowledge of structural genomic changes accompanying human evolution we still cannot identify with certainty the causative genes of human identity. Most structural gene-influential changes happened at the level of expression regulation, which in turn provoked larger alterations of interactome gene regulation networks. In this review, we summarized the available information about genetic differences between humans and chimpanzees and their potential functional impacts on differential molecular, anatomical, physiological and cognitive peculiarities of these species. -
A Minimal Set of Internal Control Genes for Gene Expression Studies in Head
bioRxiv preprint doi: https://doi.org/10.1101/108381; this version posted February 14, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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 4.0 International license. 1 A minimal set of internal control genes for gene expression studies in head 2 and neck squamous cell carcinoma. 1 1 1 2 3 Vinayak Palve , Manisha Pareek , Neeraja M Krishnan , Gangotri Siddappa , 2 2 1,3* 4 Amritha Suresh , Moni Abraham Kuriakose and Binay Panda 5 1 6 Ganit Labs, Bio-IT Centre, Institute of Bioinformatics and Applied Biotechnology, 7 Bangalore 560100 2 8 Mazumdar Shaw Cancer Centre and Mazumdar Shaw Centre for Translational 9 Research, Bangalore 560096 3 10 Strand Life Sciences, Bangalore 560024 11 * Corresponding author: [email protected] 12 13 Abstract: 14 Background: Selection of the right reference gene(s) is crucial in the analysis and 15 interpretation of gene expression data. In head and neck cancer, studies evaluating 16 the efficacy of internal reference genes are rare. Here, we present data for a minimal 17 set of candidates as internal control genes for gene expression studies in head and 18 neck cancer. 19 Methods: We analyzed data from multiple sources (in house whole-genome gene 20 expression microarrays, n=21; TCGA RNA-seq, n=42, and published gene 21 expression studies in head and neck tumors from literature) to come up with a set of 22 genes (discovery set) for their stable expression across tumor and normal tissues. -
1 UST College of Science Department of Biological Sciences
UST College of Science Department of Biological Sciences 1 Pharmacogenomics of Myofascial Pain Syndrome An Undergraduate Thesis Submitted to the Department of Biological Sciences College of Science University of Santo Tomas In Partial Fulfillment of the Requirements for the Degree of Bachelor of Science in Biology Jose Marie V. Lazaga Marc Llandro C. Fernandez May 2021 UST College of Science Department of Biological Sciences 2 PANEL APPROVAL SHEET This undergraduate research manuscript entitled: Pharmacogenomics of Myofascial Pain Syndrome prepared and submitted by Jose Marie V. Lazaga and Marc Llandro C. Fernandez, was checked and has complied with the revisions and suggestions requested by panel members after thorough evaluation. This final version of the manuscript is hereby approved and accepted for submission in partial fulfillment of the requirements for the degree of Bachelor of Science in Biology. Noted by: Asst. Prof. Marilyn G. Rimando, PhD Research adviser, Bio/MicroSem 602-603 Approved by: Bio/MicroSem 603 panel member Bio/MicroSem 603 panel member Date: Date: UST College of Science Department of Biological Sciences 3 DECLARATION OF ORIGINALITY We hereby affirm that this submission is our own work and that, to the best of our knowledge and belief, it contains no material previously published or written by another person nor material to which a substantial extent has been accepted for award of any other degree or diploma of a university or other institute of higher learning, except where due acknowledgement is made in the text. We also declare that the intellectual content of this undergraduate research is the product of our work, even though we may have received assistance from others on style, presentation, and language expression. -
CRAVAT 4: Cancer-Related Analysis of Variants Toolkit David L
Cancer Focus on Computer Resources Research CRAVAT 4: Cancer-Related Analysis of Variants Toolkit David L. Masica1,2, Christopher Douville1,2, Collin Tokheim1,2, Rohit Bhattacharya2,3, RyangGuk Kim4, Kyle Moad4, Michael C. Ryan4, and Rachel Karchin1,2,5 Abstract Cancer sequencing studies are increasingly comprehensive and level interpretation, including joint prioritization of all nonsilent well powered, returning long lists of somatic mutations that can be mutation consequence types, and structural and mechanistic visu- difficult to sort and interpret. Diligent analysis and quality control alization. Results from CRAVAT submissions are explored in an can require multiple computational tools of distinct utility and interactive, user-friendly web environment with dynamic filtering producing disparate output, creating additional challenges for the and sorting designed to highlight the most informative mutations, investigator. The Cancer-Related Analysis of Variants Toolkit (CRA- even in the context of very large studies. CRAVAT can be run on a VAT) is an evolving suite of informatics tools for mutation inter- public web portal, in the cloud, or downloaded for local use, and is pretation that includes mutation mapping and quality control, easily integrated with other methods for cancer omics analysis. impact prediction and extensive annotation, gene- and mutation- Cancer Res; 77(21); e35–38. Ó2017 AACR. Background quickly returning mutation interpretations in an interactive and user-friendly web environment for sorting, visualizing, and An investigator's work is far from over when results are returned inferring mechanism. CRAVAT (see Supplementary Video) is from the sequencing center. Depending on the service, genetic suitable for large studies (e.g., full-exome and large cohorts) mutation calls can require additional mapping to include all and small studies (e.g., gene panel or single patient), performs relevant RNA transcripts or correct protein sequences. -
Identification of Cis-Regulatory Sequence
Worsley-Hunt et al. Genome Medicine 2011, 3:65 http://genomemedicine.com/content/3/9/65 REVIEW Identication of cis-regulatory sequence variations in individual genome sequences Rebecca Worsley-Hunt1,2, Virginie Bernard1 and Wyeth W Wasserman1* Abstract for the appropriate patterning or magnitude of gene expression. Similarly, mutations can disrupt other sequence- Functional contributions of cis-regulatory sequence specific regulatory controls, such as elements regulating variations to human genetic disease are numerous. For RNA splicing or stability. Although much emphasis in the instance, disrupting variations in a HNF4A transcription age of exome sequencing has been placed on variation factor binding site upstream of the Factor IX gene within protein-encoding sequences, it is apparent that contributes causally to hemophilia B Leyden. Although regulatory sequence disruptions will become a key focus clinical genome sequence analysis currently focuses as full genome sequences become widely accessible for on the identication of protein-altering variation, the medical genetics research. impact of cis-regulatory mutations can be similarly e emerging collection of cis-regulatory variations strong. New technologies are now enabling genome that cause human disease or altered phenotype is grow- sequencing beyond exomes, revealing variation across ing [2-4]. Reports identify cis-acting, expression-altering the non-coding 98% of the genome responsible for mutations observed within introns, far upstream of developmental and physiological patterns of gene genes, at splicing sites or within microRNA target sites. activity. The capacity to identify causal regulatory For example, cis-regulatory mutations have roles in hemo- mutations is improving, but predicting functional philia, Gilbert’s syndrome, Bernard-Soulier syndrome, changes in regulatory DNA sequences remains a great irritable bowel syndrome, beta-thalassemia, cholesterol challenge. -
Transcriptome-Wide Profiling of Cerebral Cavernous Malformations
www.nature.com/scientificreports OPEN Transcriptome-wide Profling of Cerebral Cavernous Malformations Patients Reveal Important Long noncoding RNA molecular signatures Santhilal Subhash 2,8, Norman Kalmbach3, Florian Wegner4, Susanne Petri4, Torsten Glomb5, Oliver Dittrich-Breiholz5, Caiquan Huang1, Kiran Kumar Bali6, Wolfram S. Kunz7, Amir Samii1, Helmut Bertalanfy1, Chandrasekhar Kanduri2* & Souvik Kar1,8* Cerebral cavernous malformations (CCMs) are low-fow vascular malformations in the brain associated with recurrent hemorrhage and seizures. The current treatment of CCMs relies solely on surgical intervention. Henceforth, alternative non-invasive therapies are urgently needed to help prevent subsequent hemorrhagic episodes. Long non-coding RNAs (lncRNAs) belong to the class of non-coding RNAs and are known to regulate gene transcription and involved in chromatin remodeling via various mechanism. Despite accumulating evidence demonstrating the role of lncRNAs in cerebrovascular disorders, their identifcation in CCMs pathology remains unknown. The objective of the current study was to identify lncRNAs associated with CCMs pathogenesis using patient cohorts having 10 CCM patients and 4 controls from brain. Executing next generation sequencing, we performed whole transcriptome sequencing (RNA-seq) analysis and identifed 1,967 lncRNAs and 4,928 protein coding genes (PCGs) to be diferentially expressed in CCMs patients. Among these, we selected top 6 diferentially expressed lncRNAs each having signifcant correlative expression with more than 100 diferentially expressed PCGs. The diferential expression status of the top lncRNAs, SMIM25 and LBX2-AS1 in CCMs was further confrmed by qRT-PCR analysis. Additionally, gene set enrichment analysis of correlated PCGs revealed critical pathways related to vascular signaling and important biological processes relevant to CCMs pathophysiology. -
Supplemental Information
Supplemental information Dissection of the genomic structure of the miR-183/96/182 gene. Previously, we showed that the miR-183/96/182 cluster is an intergenic miRNA cluster, located in a ~60-kb interval between the genes encoding nuclear respiratory factor-1 (Nrf1) and ubiquitin-conjugating enzyme E2H (Ube2h) on mouse chr6qA3.3 (1). To start to uncover the genomic structure of the miR- 183/96/182 gene, we first studied genomic features around miR-183/96/182 in the UCSC genome browser (http://genome.UCSC.edu/), and identified two CpG islands 3.4-6.5 kb 5’ of pre-miR-183, the most 5’ miRNA of the cluster (Fig. 1A; Fig. S1 and Seq. S1). A cDNA clone, AK044220, located at 3.2-4.6 kb 5’ to pre-miR-183, encompasses the second CpG island (Fig. 1A; Fig. S1). We hypothesized that this cDNA clone was derived from 5’ exon(s) of the primary transcript of the miR-183/96/182 gene, as CpG islands are often associated with promoters (2). Supporting this hypothesis, multiple expressed sequences detected by gene-trap clones, including clone D016D06 (3, 4), were co-localized with the cDNA clone AK044220 (Fig. 1A; Fig. S1). Clone D016D06, deposited by the German GeneTrap Consortium (GGTC) (http://tikus.gsf.de) (3, 4), was derived from insertion of a retroviral construct, rFlpROSAβgeo in 129S2 ES cells (Fig. 1A and C). The rFlpROSAβgeo construct carries a promoterless reporter gene, the β−geo cassette - an in-frame fusion of the β-galactosidase and neomycin resistance (Neor) gene (5), with a splicing acceptor (SA) immediately upstream, and a polyA signal downstream of the β−geo cassette (Fig. -
Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia
Published OnlineFirst September 20, 2013; DOI: 10.1158/2159-8290.CD-13-0350 RESEARCH ARTICLE Individualized Systems Medicine Strategy to Tailor Treatments for Patients with Chemorefractory Acute Myeloid Leukemia Tea Pemovska 1 , Mika Kontro 2 , Bhagwan Yadav 1 , Henrik Edgren 1 , Samuli Eldfors1 , Agnieszka Szwajda 1 , Henrikki Almusa 1 , Maxim M. Bespalov 1 , Pekka Ellonen 1 , Erkki Elonen 2 , Bjørn T. Gjertsen5 , 6 , Riikka Karjalainen 1 , Evgeny Kulesskiy 1 , Sonja Lagström 1 , Anna Lehto 1 , Maija Lepistö1 , Tuija Lundán 3 , Muntasir Mamun Majumder 1 , Jesus M. Lopez Marti 1 , Pirkko Mattila 1 , Astrid Murumägi 1 , Satu Mustjoki 2 , Aino Palva 1 , Alun Parsons 1 , Tero Pirttinen 4 , Maria E. Rämet 4 , Minna Suvela 1 , Laura Turunen 1 , Imre Västrik 1 , Maija Wolf 1 , Jonathan Knowles 1 , Tero Aittokallio 1 , Caroline A. Heckman 1 , Kimmo Porkka 2 , Olli Kallioniemi 1 , and Krister Wennerberg 1 ABSTRACT We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profi ling and ex vivo drug sensitivity and resistance testing (DSRT) of patients’ cancer cells to 187 oncology drugs, (ii) clinical implementation of therapies predicted to be effective, and (iii) studying consecutive samples from the treated patients to understand the basis of resistance. Here, application of ISM to 28 samples from patients with acute myeloid leukemia (AML) uncovered fi ve major taxonomic drug-response sub- types based on DSRT profi les, some with distinct genomic features (e.g., MLL gene fusions in subgroup IV and FLT3 -ITD mutations in subgroup V). Therapy based on DSRT resulted in several clinical responses. -
Large-Scale Rnai Screening Uncovers New Therapeutic Targets in the Human Parasite
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.05.935833; this version posted February 6, 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 4.0 International license. 1 Large-scale RNAi screening uncovers new therapeutic targets in the human parasite 2 Schistosoma mansoni 3 4 Jipeng Wang1*, Carlos Paz1*, Gilda Padalino2, Avril Coghlan3, Zhigang Lu3, Irina Gradinaru1, 5 Julie N.R. Collins1, Matthew Berriman3, Karl F. Hoffmann2, James J. Collins III1†. 6 7 8 1Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas 75390 9 2Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, 10 Aberystwyth, Wales, UK. 11 3Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK 12 *Equal Contribution 13 14 15 16 17 18 19 20 21 22 23 †To whom correspondence should be addressed 24 [email protected] 25 UT Southwestern Medical Center 26 Department of Pharmacology 27 6001 Forest Park. Rd. 28 Dallas, TX 75390 29 United States of America bioRxiv preprint doi: https://doi.org/10.1101/2020.02.05.935833; this version posted February 6, 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 4.0 International license. 30 ABSTRACT 31 Schistosomes kill 250,000 people every year and are responsible for serious morbidity in 240 32 million of the world’s poorest people. -
Mirna‑26A‑5P and Mir‑26B‑5P Inhibit the Proliferation of Bladder Cancer Cells by Regulating PDCD10
ONCOLOGY REPORTS 40: 3523-3532, 2018 miRNA‑26a‑5p and miR‑26b‑5p inhibit the proliferation of bladder cancer cells by regulating PDCD10 KE WU1*, XING-YU MU1*, JUN-TAO JIANG1, MING-YUE TAN1, REN-JIE WANG1, WEN-JIE ZHOU2, XIANG WANG1, YIN-YAN HE3, MING-QING LI2 and ZHI-HONG LIU1 1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080; 2Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011; 3Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China Received October 11, 2017; Accepted September 4, 2018 DOI: 10.3892/or.2018.6734 Abstract. MicroRNA (miR)-26a-5p and miR-26b-5p consis- and miR-26b-5p were pivotal regulators in BC progression tently play an antitumor role in many types of cancers, but the by targeting the proliferation-related protein, PDCD10. The underlying mechanism remains unclear in bladder cancer (BC). miR-26-5p/PDCD10 interaction may provide important In the present study, we found that, in BC tissues, the levels of insight into the pathway of BC progression and present novel miR-26a-5p and miR-26b-5p were lower than in paired normal opportunities for future diagnosis and treatment strategies, tissues. The upregulation of miR‑26‑5p significantly inhibited especially for patients with high levels of PDCD10. the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) Introduction was the downstream target gene of miR-26a-5p/miR-26b-5p, and this was ascertained by western blotting and quantitative Bladder cancer (BC) is one of the most important urinary real-time reverse transcription PCR (RT-qPCR). -
862F50a0ea63c82ca473bf845b5
Brain region Type Enriched GO annotation Gene symbol AQR, ARMC7, BTBD9, HACL1, KCTD10, KCTD13, LSM6, MT2A, MYBPC1, POLD2, SRPX, TNFAIP1, USP25, EC Common type DNA replication, Protein catabolic process, Transport USP28, ZMYND19 EC Common type Transport KIAA1549, MBD5, MYO5B, RAB11A, RAB11FIP1, RAB11FIP2, RAB11FIP3, RAB11FIP4, RAB11FIP5, REPS1 ACD, BMP2K, C1orf63, CDK13, CLK3, CYLC2, DDX3Y, FOXJ3, GNL3L, GRPEL1, KIAA2022, MACROD2, Cellular component organization, Kinase activity, Localization, EC Common type NANOG, PAK1IP1, PCBP1, PCMT1, PLOD1, PLOD2, POT1, PRPS1L1, RASGEF1C, RBM15B, RPS7, RSBN1L, Response to stimulus, Transcription SALL1, SEC16A, TDRD6, TERF1, TERF2IP, TINF2, YTHDF1, YTHDF3, ZC3HAV1L, ZNF281 AGFG1, AKR1C3, ARIH1, ARIH2, BCL10, BFAR, BIRC2, BIRC3, BIRC6, BIRC7, C9orf89, CADPS2, CNOT4, DDX58, DIABLO, DTX1, DTX3L, DZIP3, EIF4E2, EML4, EPS15, EXTL3, FBXL19, FCHO2, GPR108, HLTF, HPCA, HTRA2, INF2, ISG15, KIAA1107, KIAA1797, LNX2, LOC147791, LRSAM1, LTN1, MAGEL2, MAP3K1, MARCH5, MARCH7, MC1R, MFN1, MGRN1, MID1, MID2, MKRN1, MKRN2, MKRN3, MRAP, MUL1, NAIP, PARP9, PCNP, PDZRN3, PJA2, PLCD4, RBCK1, RLIM, RMND5B, RNF10, RNF103, RNF11, RNF111, RNF114, DNA repair, Apoptosis, Protein catabolic process, Protein EC Common type RNF115, RNF125, RNF126, RNF128, RNF13, RNF130, RNF138, RNF14, RNF144A, RNF150, RNF165, RNF166, metabolic process, Protein modification process RNF167, RNF181, RNF182, RNF25, RNF26, RNF38, RNF4, RNF41, RSPRY1, SGCE, SH3RF2, STRADB, TMBIM6, TMEM189, TOPORS, TRAF7, TRIM2, TRIM25, TRIM26, TRIM27, TRIM32, TRIM35, TRIM39, -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement.