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Join us as we welcome back Dr. Veera Rajagopal, a discovery scientist at Regeneron with an interest in human genetics and drug target discovery in neuroscience and psychiatry. If you're a regular listener of The Genetics Podcast, you are likely familiar with Dr. Veera's annual round-up episodes. This year, we are excited to announce quarterly episodes with Dr. Veera, where he and Patrick walk you through the latest developments in genetics, drug discovery, and precision medicine throughout the year. This quarter's episode will focus on non-coding variants and the future of genome-wide association studies (GWAS). Tune in now, and don't forget to check out Veera's substack, GWAS Stories, and his Twitter, @doctorveera.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.29.551032v1?rss=1 Authors: Sun, C., Zhou, C., Daneshvar, K., Kratkiewicz, A. J., Ben Saad, A., Hess, A., Chen, J. Y., Pondick, J. V., York, S. R., Li, W., Moran, S. P., Gentile, S., Ur Rahman, R., Li, Z., Sparks, R., Habboub, T., Kim, B.-M., Choi, M., Affo, S., Schwabe, R. F., Popov, Y. V., Mullen, A. C. Abstract: Background & Aims: Fibrosis is the common endpoint for all forms of chronic liver injury, and progression of fibrosis leads to the development of end-stage liver disease. Activation of hepatic stellate cells (HSCs) and their transdifferentiation to myofibroblasts results in the accumulation of the extracellular matrix (ECM) proteins that form the fibrotic scar. Long noncoding (lnc) RNAs regulate the activity of HSCs and may provide targets for fibrotic therapies. Methods: We identified lncRNA TILAM as expressed near COL1A1 in human HSCs and performed loss-of-function studies in human HSCs and liver organoids. Transcriptomic analysis of HSCs isolated from mice defined the murine ortholog of TILAM. We then generated Tilam-deficient GFP reporter mice and quantified fibrotic responses to carbon tetrachloride (CCl4) and choline-deficient L-amino acid defined high fat diet (CDA-HFD). Co-precipitation studies, mass spectrometry, and gene expression analyses identified protein partners of TILAM. Results: TILAM is conserved between human and mouse HSCs and regulates expression of ECM proteins, including collagen. Tilam is selectively induced in murine HSCs during the development of fibrosis in vivo. In both male and female mice, loss of Tilam results in reduced fibrosis in the setting of CCl4 and CDA-HFD injury models. TILAM interacts with promyelocytic leukemia protein (PML) to stabilize PML protein levels and promote the fibrotic activity of HSCs. Conclusion: TILAM is activated in HSCs and interacts with PML to drive the development of liver fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end stage liver disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
This week, hosts Facundo Lodol and Mark Ambrogio interview Biology PhD candidate Matheus Sanita Lima. Matheus talks about how noncoding DNA might have important biological functions. He studies noncoding DNA segments in the genomes of mitocondria and chloroplasts. To find out more about Matheus' research, check out his lab's website here. Recorded on May 16, 2023 Produced by Jordan VanderBurgt Theme song provided by https://freebeats.io/ Produced by White Hot.
The vast stretches of DNA that don't code for proteins could fill key knowledge gaps about autism genetics. But making sense of it all won't be easy. The post The final frontier: Autism geneticists take on the noncoding genome appeared first on Spectrum | Autism Research News.
The vast stretches of DNA that don’t code for proteins could fill key knowledge gaps about autism genetics. But making sense of it all won’t be easy.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.16.385633v1?rss=1 Authors: Chen, L., Jiang, Y., Yao, B., Huang, K., Liu, Y., Wang, Y., Qin, X., Saykin, A. J., Wang, Y. Abstract: Understanding the functional consequence of noncoding variants is of great interest. Though genome-wide association studies (GWAS) or quantitative trait locus (QTL) analyses have identified variants associated with traits or molecular phenotypes, most of them are located in the noncoding regions, making the identification of causal variants a particular challenge. Existing computational approaches developed for for prioritizing non- coding variants produce inconsistent and even conflicting results. To address these challenges, we propose a novel statistical learning framework, which directly integrates the precomputed functional scores from representative scoring methods. It will maximize the usage of integrated methods by automatically learning the relative contribution of each method and produce an ensemble score as the final prediction. The framework consists of two modes. The first "context-free" mode is trained using curated causal regulatory variants from a wide range of context and is applicable to predict noncoding variants of unknown and diverse context. The second "context-dependent" mode further improves the prediction when the training and testing variants are from the same context. By evaluating the framework via both simulation and empirical studies, we demonstrate that it outperforms integrated scoring methods and the ensemble score successfully prioritizes experimentally validated regulatory variants in multiple risk loci. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.27.315507v1?rss=1 Authors: Liu, B., Thippabhotla, S., Zhang, J., Zhong, C. Abstract: Noncoding RNA plays important regulatory and functional roles in microorganisms, such as gene expression regulation, signaling, protein synthesis, and RNA processing. Given its essential role in microbial physiology, it is natural to question whether we can use noncoding RNAs as biomarkers to distinguish among environments under different biological conditions, such as those between healthy versus disease status. The current metagenomic sequencing technology primarily generates short reads, which contain incomplete structural information that may complicate noncoding RNA homology detection. On the other hand, de novo assembly of the metagenomics sequencing data remains fragmentary and has a risk of missing low-abundant noncoding RNAs. To tackle these challenges, we have developed DRAGoM (Detection of RNA using Assembly Graph from Metagenomics data), a novel noncoding RNA homology search algorithm. DRAGoM operates on a metagenome assembly graph, rather than on unassembled reads or assembled contigs. Our benchmark experiments show DRAGoM's improved performance and robustness over the traditional approaches. We have further demonstrated DRAGoM's real-world applications in disease characterization via analyzing a real case-control gut microbiome dataset for Type-2 diabetes (T2D). DRAGoM revealed potential ncRNA biomarkers that can clearly separate the T2D gut microbiome from those of healthy controls. DRAGoM is freely available from https://github.com/benliu5085/DRAGoM. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.247007v1?rss=1 Authors: Rasmussen, A. W., Äijö, T., Gabitto, M. I., Carriero, N., Sanjana, N., Skok, J., Bonneau, R. Abstract: Clustered Regularly Interspace Short Palindromic Repeats (CRISPR)-Cas9 genome editing methods provide the tools necessary to examine phenotypic impacts of targeted perturbations in high-throughput screens. While these technologies have the potential to reveal functional elements with direct therapeutic applications, statistical techniques to analyze noncoding screen data remain limited. We present CRISPR-Decryptr, a computational tool for the analysis of CRISPR noncoding screens. Our method leverages experimental design: accounting for multiple conditions, controls, and replicates to infer the regulatory landscape of noncoding genomic regions. We validate our method on a variety of mutagenesis, CRISPR activation, and CRISPR interference screens, extracting new insights from previously published data. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.16.087395v1?rss=1 Authors: Asgari, Y., Heng, J. I.-T., Lovell, N., Forrest, A., Alinejad-Rokny, H. Abstract: Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment and in diseases is poorly understood. In this study, we have performed a genome-wide investigation of human noncoding RNAs for cell regulatory functions in brain tissue. By analysing ENCODE regulatory features, associations with FANTOM5 tissue-specific enhancers, as well as tissue-specific expression profiles, we have identified 17,743 noncoding RNAs comprising at least one nervous system-related expression Quantitative Trait Loci (eQTL) polymorphism that is associated with protein coding genes. Of these, 908 brain-enriched noncoding RNAs (comprising 907 long noncoding RNAs and 1 pseudogene) also overlap with chromatin states characterised as enhancers. Based on these criteria, we referred to such noncoding RNAs with putative enhancer activity as brain "enhancer-ncRNAs". To investigate their impact in neurodevelopmental disorders, we integrated GWAS SNPs and Copy Number Variation (CNV) data and found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs. However, in 23 of these 82 enhancer-ncRNAs, eQTL interaction was explained solely by the presence of each of these noncoding RNAs, suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. We also cross-referenced our data with the DECIPHER database of clinical phenotypes to find that mutations to 34 of the 82 enhancer-ncRNAs are significantly associated with phenotypes including behavioural abnormality, and cognitive impairment. Taken together, we provide evidence for a distinct set of brain-enriched ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders. Copy rights belong to original authors. Visit the link for more info
From the University of Texas at Austin, Vincent and Rich speak with Chris Sullivan about his work on miRNAs encoded in the genomes of polyomaviruses and papillomaviruses, and how an RNA triphosphatase restricts hepatitis C virus replication. Hosts: Vincent Racaniello and Rich Condit Guest: Chris Sullivan Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Sullivan lab Virus-encoded miRNAs in papillomaviruses (PLoS Path) Murine polyomavirus miRNA promotes viruria (J Virol) DUSP11 helps XRN restrict hepatitis C virus (PNAS) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
From the University of Texas at Austin, Vincent and Rich speak with Chris Sullivan about his work on miRNAs encoded in the genomes of polyomaviruses and papillomaviruses, and how an RNA triphosphatase restricts hepatitis C virus replication. Hosts: Vincent Racaniello and Rich Condit Guest: Chris Sullivan Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Sullivan lab Virus-encoded miRNAs in papillomaviruses (PLoS Path) Murine polyomavirus miRNA promotes viruria (J Virol) DUSP11 helps XRN restrict hepatitis C virus (PNAS) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
Nels and Vincent explore the evolution of new protein-coding genes de novo from nocoding DNA sequences, using the antifreeze protein of northern codfish as a model. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiEVO Evolution of antifreeze protein gene in codfish (PNAS) Codfish diversity (Cheng lab) Frankentomatoes (Huff Post) Image credit Time stamps by Jolene. Thanks! Science Picks Nels- Science at Sundance reviews Vincent- The Rise and Fall of Scientific Authority Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv
The ImmuNerds discuss how a cellular long non-coding RNA binds to an innate RNA sensor and regulates virus-induced interferon production to prevent damage to the host. Hosts: Vincent Racaniello, Stephanie Langel, and Cynthia Leifer Subscribe (free): iTunes, Google Podcasts. RSS, email Become a patron of Immune! Links for this episode Host lncRNA binds RIG-I (Cell) Microbe Art at virology blog Letters read on Immune 13 Time stamps by Jolene. Thanks! Weekly Science Picks Steph- That's Pediatrics Podcast Cindy- Trilobite Glassworks Vincent- Research!America Music by Steve Neal. Immune logo image by Blausen Medical. Send your immunology questions and comments to immune@microbe.tv
Commentary by Dr. Valentin Fuster
Thierry Pedrazzini, Lausanne University, Switzerland, speaks on "Control of cardiac cell identity and behaviour via targeting long noncoding RNAs". This movie has been recorded at ICGEB Trieste and is part of "RNA structure and function" Course 2018.
Nels joins the TWiV team to talk about his work on genomic accordions in vaccinia virus, hepatitis B virus in a 439 year old mummy, and viral induction of energy synthesis by a long noncoding RNA. Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Guest: Nels Elde Click arrow to play Download TWiV 476 (63 MB .mp3, 105 min) Subscribe (free): iTunes, RSS, email Become a patron of TWiV! Links for this episode ASV 2018: asv.org, asv2018.umd.edu TWiV is a must-listen (WaPo) More on poxvirus accordions (bioRxiv) HBV from a 439 year old mummy (PLoS Path) lncRNA promotes viral replication by inducing metabolism (Science) Making Data Visual Letters read on TWiV 476 Weekly Science Picks Nels - Everyday Evolution Kathy - Paper-fold an ellipse Rich - Oxford Nanopore Technologies: YouTube channel; General technology; DNA sequencing; Sequencing singularity Dickson - Spiders that look like pelicans Alan - Guessing pool for China Spacelab reentry Vincent - How to take a picture of the stealth bomber over the rose bowl Listener Picks Gretchen - The Bearded Lady Project Intro music is by Ronald Jenkees. Send your virology questions and comments to twiv@microbe.tv
G. Biamonti, Istituto di Genetica Biochimica ed Evoluzionistica, CNR, Pavia - ITALY speaks on "Long-noncoding Satellite III RNAs and defects in chromosome migration during mitosis". This seminar has been recorded by ICGEB Trieste
Alena Shkumatava, Génétique et Biologie du Développement, Institut Curie - Centre de Recherche, Paris - FRANCE speaks on "Vertebrate long noncoding RNAs: Functions, Mechanisms and Evolution". This seminar has been recorded by ICGEB Trieste
Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler Guest: Scott Tibbetts Scott Tibbetts joins the TWiVists to describe his work on the role of a herpesviral nocoding RNA in establishment of peripheral latency, and then we visit two last minute additions to the Zika virus literature. Links for this episode Noncoding RNA required for establishment of latency (mSphere) 17:20 Lessons learned from in vivo studies of a viral noncoding RNA (mSphere) 1:05:05 Zika virus in pregnant women in Rio de Janeiro (NEJM) 1:06:10 Zika virus infects cortical neural progenitors (Cell Stem Cell) 1:12:00 Image credit Letters read on TWiV 379 1:15:10 This episode is sponsored by 32nd Clinical Virology Symposium and Microbe Magazine Podcast 4:15, 1:05:25 Weekly Science Picks 1:42:45 Alan - Okeanos ExplorerDickson - Rome RebornVincent - Twitter Missing ManualScott - Best Science Images of 2015Kathy - Space Travel PostersRich - GoISSWatch Listener Pick Peter - Antibiotics and the Problem of the Broken Market Send your virology questions and comments to twiv@microbe.tv
Hosts: Vincent Racaniello, Rich Condit, and Kathy Spindler Guest: Joan Steitz This episode was recorded at the 34th Annual Meeting of the American Society for Virology, where Vincent, Rich, and Kathy spoke with Joan Steitz, a tireless promoter of women in science and one of the greatest scientists of our generation. Links for this episode ASV annual meeting, Western University Steitz Laboratory at Yale University Steitz Laboratory on Twitter Panoramic photo of ASV TWiV by Matt Evans Photos of ASV2015 (Facebook) Video of this episode - view at YouTube Weekly Science Picks Kathy - Charity HallRich - Ribosome binding sites of phage R17 mRNAVincent - Pluto flyby Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv
Listen to Ashutosh Dharap discuss his latest ASN NEURO paper on increased binding of stroke-induced long non-coding RNAs to the transcriptional corepressors Sin3A and coREST.
Valerio Orlando, Dulbecco Telethon Institute, Epigenetics and Genome Reprogramming lab., IRCCS Fondazone S. Lucia, Rome, ITALY speaks on "Role of noncoding genome in epigenetic control of cell identity". This seminar has been recorded by ICGEB Trieste
Six Buschke-Löwenstein tumors, i.e., highly differentiated squamous cell tumors of the genital region, were shown to contain human papillomavirus 6 (HPV 6) or HPV 11 genomes. The viral DNA was found in an episomal state, including a very small fraction of circular oligomers. HPV 6a and HPV 6d genomes were cloned from two of the tumors. Comparison with HPV 6b, cloned from a benign genital wart (E. -M. de Villiers, L. Gissmann, and H. zur Hausen, J. Virol. 40:932-935, 1981) by restriction mapping and partial sequence analysis, revealed a very high degree of homology with the different HPV 6 subtypes. A tandem duplication of 459 base pairs within the noncoding region of the genome was found in the new subtype HPV 6d. This structural rearrangement in a region containing the putative control elements for early gene transcription might influence the biological potential of that virus. No evidence for rearrangement of this region was found in the HPV DNA from the five other tumors.
Thierry Pedrazzini, Experimental Cardiology Unit Department of Medicine University of Lausanne Medical School Lausanne, Lausanne, SWITZERLAND speaks on "Importance of long noncoding RNAs in cardiac homeostasis". This seminar has been recorded by ICGEB