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  1. Article ; Online: Dual RNA-Seq analysis of SARS-CoV-2 correlates specific human transcriptional response pathways directly to viral expression.

    Maulding, Nathan D / Seiler, Spencer / Pearson, Alexander / Kreusser, Nicholas / Stuart, Joshua M

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 1329

    Abstract: The SARS-CoV-2 pandemic has challenged humankind's ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying ... ...

    Abstract The SARS-CoV-2 pandemic has challenged humankind's ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus evolve, or future coronaviruses may emerge that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of the previously developed "dual RNA-seq" approach to investigate, for the first time, the co-regulation between the human and SARS-CoV-2 transcriptomes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL's, SPRR's, S100's with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings highlight unappreciated SARS-CoV-2 expression signatures and emphasize new considerations and mechanisms for SARS-CoV-2 therapeutic intervention.
    MeSH term(s) A549 Cells ; COVID-19/genetics ; COVID-19/metabolism ; Gene Expression Regulation, Viral ; Humans ; RNA-Seq ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Transcriptome
    Language English
    Publishing date 2022-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-05342-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dual RNA-Seq analysis of SARS-CoV-2 correlates specific human transcriptional response pathways directly to viral expression

    Nathan D. Maulding / Spencer Seiler / Alexander Pearson / Nicholas Kreusser / Joshua M. Stuart

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Abstract The SARS-CoV-2 pandemic has challenged humankind’s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, ... ...

    Abstract Abstract The SARS-CoV-2 pandemic has challenged humankind’s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus evolve, or future coronaviruses may emerge that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of the previously developed “dual RNA-seq” approach to investigate, for the first time, the co-regulation between the human and SARS-CoV-2 transcriptomes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL’s, SPRR’s, S100’s with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings highlight unappreciated SARS-CoV-2 expression signatures and emphasize new considerations and mechanisms for SARS-CoV-2 therapeutic intervention.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Dual RNA-Seq analysis of SARS-CoV-2 correlates specific human transcriptional response pathways directly to viral expression

    Maulding, Nathan D / Seiler, Spencer / Pearson, Alex / Kreusser, Nicholas / Stuart, Josh

    bioRxiv

    Abstract: The SARS-CoV-2 pandemic has challenged humankind9s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying ... ...

    Abstract The SARS-CoV-2 pandemic has challenged humankind9s ability to quickly determine the cascade of health effects caused by a novel infection. Even with the unprecedented speed at which vaccines were developed and introduced into society, identifying therapeutic interventions and drug targets for patients infected with the virus remains important as new strains of the virus may evolve, or future coronaviruses may emerge, that are resistant to current vaccines. The application of transcriptomic RNA sequencing of infected samples may shed new light on the pathways involved in viral mechanisms and host responses. We describe the application of "dual RNA-seq" analysis to consider both the host and pathogen transcriptomes simultaneously, to investigate for the first time the co-regulation of human and SARS-CoV-2 genes. Together with differential expression analysis, we describe the tissue specificity of SARS-CoV-2 expression, an inferred lipopolysaccharide response, and co-regulation of CXCL9s, SPRR9s, S1009s with SARS-CoV-2 expression. Lipopolysaccharide response pathways in particular offer promise for future therapeutic research and the prospect of subgrouping patients based on chemokine expression that may help explain the vastly different reactions patients have to infection. Taken together these findings illuminate previously unappreciated SARS-CoV-2 expression signatures, identify new therapeutic considerations, and contribute a pipeline for studying multi-transcriptome systems.
    Keywords covid19
    Language English
    Publishing date 2021-02-09
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.02.09.430517
    Database COVID19

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  4. Article ; Online: Genetic pathways disrupted by ENPP1 deficiency provide insight into mechanisms of osteoporosis, osteomalacia, and paradoxical mineralization.

    Maulding, Nathan D / Kavanagh, Dillon / Zimmerman, Kristin / Coppola, Gianfilippo / Carpenter, Thomas O / Jue, Nathaniel K / Braddock, Demetrios T

    Bone

    2020  Volume 142, Page(s) 115656

    Abstract: Ectonucleotide phosphatase/phosphodiesterase 1 (ENPP1) deficiency results in either lethal arterial calcifications ('Generalized Arterial Calcification of Infancy' - GACI), phosphate wasting rickets ('Autosomal Recessive Hypophosphatemic Rickets type 2' - ...

    Abstract Ectonucleotide phosphatase/phosphodiesterase 1 (ENPP1) deficiency results in either lethal arterial calcifications ('Generalized Arterial Calcification of Infancy' - GACI), phosphate wasting rickets ('Autosomal Recessive Hypophosphatemic Rickets type 2' - ARHR2), early onset osteoporosis, or progressive spinal rigidity ('Ossification of the Posterior Longitudinal Ligament' - OPLL). As ENPP1 generates a strong endogenous mineralization inhibitor - extracellular pyrophosphate (PPi) - ENPP1 deficiency should not result in reduced bone volume, and therefore the mechanism ENPP1 associated osteoporosis is not apparent given current understanding of the enzyme's function. To investigate genetic pathways driving the skeletal phenotype of ENPP1 deficiency we compared gene expression in Enpp1
    MeSH term(s) Animals ; Fibroblast Growth Factor-23 ; Mice ; Osteomalacia ; Osteoporosis/genetics ; Phosphoric Diester Hydrolases/genetics ; Phosphoric Monoester Hydrolases ; Pyrophosphatases/genetics ; Vascular Calcification
    Chemical Substances FGF23 protein, human ; Fgf23 protein, mouse ; Fibroblast Growth Factor-23 (7Q7P4S7RRE) ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2020-09-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 632515-4
    ISSN 1873-2763 ; 8756-3282
    ISSN (online) 1873-2763
    ISSN 8756-3282
    DOI 10.1016/j.bone.2020.115656
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The UCSC SARS-CoV-2 Genome Browser.

    Fernandes, Jason D / Hinrichs, Angie S / Clawson, Hiram / Gonzalez, Jairo Navarro / Lee, Brian T / Nassar, Luis R / Raney, Brian J / Rosenbloom, Kate R / Nerli, Santrupti / Rao, Arjun A / Schmelter, Daniel / Fyfe, Alastair / Maulding, Nathan / Zweig, Ann S / Lowe, Todd M / Ares, Manuel / Corbet-Detig, Russ / Kent, W James / Haussler, David /
    Haeussler, Maximilian

    Nature genetics

    2020  Volume 52, Issue 10, Page(s) 991–998

    MeSH term(s) Betacoronavirus/genetics ; COVID-19 ; Coronavirus Infections/virology ; Databases, Genetic ; Genome, Viral/genetics ; Humans ; Internet ; Pandemics ; Pneumonia, Viral/virology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-09-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-020-0700-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The UCSC Genome Browser database: 2021 update.

    Navarro Gonzalez, Jairo / Zweig, Ann S / Speir, Matthew L / Schmelter, Daniel / Rosenbloom, Kate R / Raney, Brian J / Powell, Conner C / Nassar, Luis R / Maulding, Nathan D / Lee, Christopher M / Lee, Brian T / Hinrichs, Angie S / Fyfe, Alastair C / Fernandes, Jason D / Diekhans, Mark / Clawson, Hiram / Casper, Jonathan / Benet-Pagès, Anna / Barber, Galt P /
    Haussler, David / Kuhn, Robert M / Haeussler, Maximilian / Kent, W James

    Nucleic acids research

    2020  Volume 49, Issue D1, Page(s) D1046–D1057

    Abstract: For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. As the field of genomics grows and more data become available, ... ...

    Abstract For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to the research community. As the field of genomics grows and more data become available, new modes of display are required to accommodate new technologies. New features released this past year include a Hi-C heatmap display, a phased family trio display for VCF files, and various track visualization improvements. Striving to keep data up-to-date, new updates to gene annotations include GENCODE Genes, NCBI RefSeq Genes, and Ensembl Genes. New data tracks added for human and mouse genomes include the ENCODE registry of candidate cis-regulatory elements, promoters from the Eukaryotic Promoter Database, and NCBI RefSeq Select and Matched Annotation from NCBI and EMBL-EBI (MANE). Within weeks of learning about the outbreak of coronavirus, UCSC released a genome browser, with detailed annotation tracks, for the SARS-CoV-2 RNA reference assembly.
    MeSH term(s) Animals ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/virology ; Computational Biology/methods ; Data Curation/methods ; Databases, Genetic ; Epidemics ; Genome/genetics ; Genomics/methods ; Humans ; Internet ; Mice ; Molecular Sequence Annotation/methods ; SARS-CoV-2/genetics ; SARS-CoV-2/physiology ; Software
    Language English
    Publishing date 2020-11-20
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkaa1070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human Heterozygous ENPP1 Deficiency Is Associated With Early Onset Osteoporosis, a Phenotype Recapitulated in a Mouse Model of Enpp1 Deficiency.

    Oheim, Ralf / Zimmerman, Kristin / Maulding, Nathan D / Stürznickel, Julian / von Kroge, Simon / Kavanagh, Dillon / Stabach, Paul R / Kornak, Uwe / Tommasini, Steven M / Horowitz, Mark C / Amling, Michael / Thompson, David / Schinke, Thorsten / Busse, Björn / Carpenter, Thomas O / Braddock, Demetrios T

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2019  Volume 35, Issue 3, Page(s) 528–539

    Abstract: Biallelic ENPP1 deficiency in humans induces generalized arterial calcification of infancy (GACI) and/or autosomal recessive hypophosphatemic rickets type 2 (ARHR2). The latter is characterized by markedly increased circulating FGF23 levels and renal ... ...

    Abstract Biallelic ENPP1 deficiency in humans induces generalized arterial calcification of infancy (GACI) and/or autosomal recessive hypophosphatemic rickets type 2 (ARHR2). The latter is characterized by markedly increased circulating FGF23 levels and renal phosphate wasting, but aberrant skeletal manifestations associated with heterozygous ENPP1 deficiency are unknown. Here, we report three adult men with early onset osteoporosis who presented with fractures in the thoracic spine and/or left radius, mildly elevated circulating FGF23, and hypophosphatemia. Total hip bone mineral density scans demonstrated osteoporosis (Z-score < -2.5) and HRpQCT demonstrated microarchitectural defects in trabecular and cortical bone. Next-generation sequencing revealed heterozygous loss-of-function mutations in ENPP1 previously observed as biallelic mutations in infants with GACI. In addition, we present bone mass and structure data as well as plasma pyrophosphate (PPi) data of two siblings suffering from ARHR2 in comparison to their heterozygous and wild-type family members indicative of an ENPP1 gene dose effect. The skeletal phenotype in murine Enpp1 deficiency yielded nearly identical findings. Ten-week-old male Enpp1
    MeSH term(s) Adult ; Animals ; Familial Hypophosphatemic Rickets ; Fibroblast Growth Factor-23 ; Fibroblast Growth Factors ; Humans ; Male ; Mice ; Osteoporosis/diagnostic imaging ; Osteoporosis/genetics ; Phenotype ; Phosphoric Diester Hydrolases/genetics ; Pyrophosphatases/genetics
    Chemical Substances FGF23 protein, human ; Fgf23 protein, mouse ; Fibroblast Growth Factors (62031-54-3) ; Fibroblast Growth Factor-23 (7Q7P4S7RRE) ; Phosphoric Diester Hydrolases (EC 3.1.4.-) ; ectonucleotide pyrophosphatase phosphodiesterase 1 (EC 3.1.4.1) ; Pyrophosphatases (EC 3.6.1.-)
    Language English
    Publishing date 2019-12-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.3911
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: The UCSC SARS-CoV-2 Genome Browser

    Fernandes, Jason D / Hinrichs, Angie S / Clawson, Hiram / Gonzalez, Jairo Navarro / Lee, Brian T / Nassar, Luis R / Raney, Brian J / Rosenbloom, Kate R / Nerli, Santrupti / Rao, Arjun A / Schmelter, Daniel / Fyfe, Alastair / Maulding, Nathan / Zweig, Ann S / Lowe, Todd M / Ares, Manuel / Corbet-Detig, Russ / Kent, W James / Haussler, David /
    Haeussler, Maximilian

    Nat Genet

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #752474
    Database COVID19

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  9. Article ; Online: The UCSC SARS-CoV-2 Genome Browser

    Fernandes, Jason D. / Hinrichs, Angie S. / Clawson, Hiram / Gonzalez, Jairo Navarro / Lee, Brian T. / Nassar, Luis R. / Raney, Brian J. / Rosenbloom, Kate R. / Nerli, Santrupti / Rao, Arjun A. / Schmelter, Daniel / Fyfe, Alastair / Maulding, Nathan / Zweig, Ann S. / Lowe, Todd M. / Ares, Manuel / Corbet-Detig, Russ / Kent, W. James / Haussler, David /
    Haeussler, Maximilian

    Nature Genetics

    2020  Volume 52, Issue 10, Page(s) 991–998

    Keywords Genetics ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-020-0700-8
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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