Publications by authors named "Ryan Connor"

7 Publications

  • Page 1 of 1

NCBI's Virus Discovery Codeathon: Building "FIVE" -The Federated Index of Viral Experiments API Index.

Viruses 2020 12 10;12(12). Epub 2020 Dec 10.

National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20894, USA.

Viruses represent important test cases for data federation due to their genome size and the rapid increase in sequence data in publicly available databases. However, some consequences of previously decentralized (unfederated) data are lack of consensus or comparisons between feature annotations. Unifying or displaying alternative annotations should be a priority both for communities with robust entry representation and for nascent communities with burgeoning data sources. To this end, during this three-day continuation of the Virus Hunting Toolkit codeathon series (VHT-2), a new integrated and federated viral index was elaborated. This Federated Index of Viral Experiments (FIVE) integrates pre-existing and novel functional and taxonomy annotations and virus-host pairings. Variability in the context of viral genomic diversity is often overlooked in virus databases. As a proof-of-concept, FIVE was the first attempt to include viral genome variation for HIV, the most well-studied human pathogen, through viral genome diversity graphs. As per the publication of this manuscript, FIVE is the first implementation of a virus-specific federated index of such scope. FIVE is coded in BigQuery for optimal access of large quantities of data and is publicly accessible. Many projects of database or index federation fail to provide easier alternatives to access or query information. To this end, a Python API query system was developed to enhance the accessibility of FIVE.
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http://dx.doi.org/10.3390/v12121424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764237PMC
December 2020

NCBI's Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements.

Genes (Basel) 2019 09 16;10(9). Epub 2019 Sep 16.

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda MD 20894, USA.

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon.
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http://dx.doi.org/10.3390/genes10090714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771016PMC
September 2019

Database resources of the National Center for Biotechnology Information.

Nucleic Acids Res 2019 01;47(D1):D23-D28

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts published in life science journals. The Entrez system provides search and retrieval operations for most of these data from 38 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Labs and a new sequence database search. Resources that were updated in the past year include PubMed, PMC, Bookshelf, genome data viewer, Assembly, prokaryotic genomes, Genome, BioProject, dbSNP, dbVar, BLAST databases, igBLAST, iCn3D and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
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http://dx.doi.org/10.1093/nar/gky1069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323993PMC
January 2019

Frontline Science: c-Myc regulates P-selectin glycoprotein ligand-1 expression in monocytes during HIV-1 infection.

J Leukoc Biol 2017 10 29;102(4):953-964. Epub 2017 Jun 29.

Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA;

Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P-Selectin glycoprotein ligand-1 (PSGL-1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL-1, 60 subjects, with or without HIV infection, were recruited and PSGL-1 expression in monocytes was measured. PSGL-1 was found to be up-regulated on leukocytes from HIV-infected individuals, and the physiologically relevant mediators soluble CD40 ligand (sCD40L) and glutamate were able to induce PSGL-1 transcription in human monocytes ex vivo. HIV-1 induced PSGL-1 induction, and its dependence on CD40L was validated further by use of the mouse-tropic HIV (EcoHIV) mouse model of HIV infection in C57BL/6 and CD40L knockout (KO) mice. To investigate crosstalk between the signaling cascades induced by CD40L and glutamate that lead to PSGL-1 induction, a network-based, discrete dynamic model was developed. The model reveals the MAPK pathway and oxidative stress as critical mediators of crosstalk between CD40L and glutamate-induced pathways. Importantly, the model predicted induction of the c-Myc transcription factor upon cotreatment, which was validated using transcriptomic data and pharmacologic inhibition of c-Myc. This study suggests a novel systems serology approach for translational research and reveals a mechanism for PSGL-1 transcriptional regulation, which might be leveraged to identify novel targets for therapeutic intervention.
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http://dx.doi.org/10.1189/jlb.6HI0217-043RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597517PMC
October 2017

Effects of a classroom-based yoga intervention on cortisol and behavior in second- and third-grade students: a pilot study.

J Evid Based Complementary Altern Med 2015 Jan 19;20(1):41-9. Epub 2014 Nov 19.

Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

This uncontrolled pilot study examined the effects of a classroom-based yoga intervention on cortisol concentrations and perceived behavior in children. A 10-week Yoga 4 Classrooms intervention was implemented in one second-grade and one third-grade classroom. Students' salivary cortisol responses were assessed at 3 time points. Classroom teachers also documented their perceptions of the effects of the intervention on students' cognitive, social, and emotional skills. Second, but not third, graders showed a significant decrease in baseline cortisol from before to after the intervention. Second and third graders both showed significant decreases in cortisol from before to after a cognitive task, but neither grade showed additional decreases from before to after a single yoga class. The second-grade teacher perceived significant improvements in several aspects his/her students' behavior. The third-grade teacher perceived some, but fewer, improvements in his/her students' behavior. Results suggest that school-based yoga may be advantageous for stress management and behavior.
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http://dx.doi.org/10.1177/2156587214557695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410873PMC
January 2015

Redo autograft operations after the Ross procedure.

Ann Thorac Surg 2012 May 30;93(5):1477-81; discussion 1481-22. Epub 2012 Mar 30.

Cardiopulmonary Research Science and Technology Institute and Medical City Dallas Hospital, Dallas, Texas 75230, USA.

Background: Autograft dilatation after the Ross procedure is the most common cause of late autograft failure. We looked at results after reoperation for autograft dysfunction using autograft sparing and composite root replacement techniques.

Methods: Data were abstracted from our prospectively collected Ross registry for 160 consecutive patients who underwent a Ross procedure by a single surgeon between 1994 and 2008. Follow-up records were obtained, and the last echocardiographic report after reoperation was analyzed.

Results: Autograft reoperation was necessary in 17 patients, at a median interval of 6.9 years after the original procedure. Indications for reoperation were insufficiency with autograft dilatation in 16 patients, and without dilatation in 1 patient. Surgical procedures used at reoperation included autograft reimplantation in 6 patients (35.3%), autograft remodeling procedure in 1 patient (5.9%), composite root replacement with mechanical valved conduit in 5 patients (29.4%), composite root replacement with biologic valved conduit in 3 patients (17.6%), and mechanical aortic valve replacement in 2 patients (11.8%). At a median follow-up of 5.0 years after reoperation, freedom from greater than 2+ aortic insufficiency was 100% (17 of 17 patients) in both reimplantation and replacement groups. There was 1 death after reoperation (at >14 years) related to complications from systemic lupus erythematosus. There have been no strokes after autograft reimplantation.

Conclusions: Autograft valve reimplantation and composite aortic root replacement are effective treatments for aortic root dilatation and aortic insufficiency after the Ross procedure. Echocardiographic follow-up demonstrates reasonable short-term function after autograft preservation procedures.
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http://dx.doi.org/10.1016/j.athoracsur.2012.01.100DOI Listing
May 2012

Potential intra- and intermolecular interactions involving the unique-5' region of the HIV-1 5'-UTR.

Biochemistry 2008 Dec;47(49):13064-73

Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250, USA.

The 5'-untranslated region (5'-UTR) of the human immunodeficiency virus type-1 (HIV-1) genome regulates multiple RNA-dependent functions during viral replication and has been proposed to adopt multiple secondary structures. Recent phylogenetic studies identified base pair complementarity between residues of the unique 5' element and those near the gag start codon (gag(AUG)) that is conserved among evolutionarily distant retroviruses, suggesting a potential long-range RNA-RNA interaction. However, nucleotide accessibility studies led to conflicting conclusions about the presence of such interactions in virions and in infected cells. Here, we show that an 11-nucleotide oligo-RNA spanning residues 105-115 of the 5'-UTR (U5) readily binds to oligoribonucleotides containing the gag start codon (AUG), disrupting a pre-existing stem loop and forming a heteroduplex stabilized by 11 Watson-Crick base pairs (K(d) = 0.47 +/- 0.16 microM). Addition of the HIV-1 nucleocapsid protein (NC), the trans-acting viral factor required for genome packaging, disrupts the heteroduplex by binding tightly to U5 (K(d) = 122 +/- 10 nM). The structure of the NC:U5 complex, determined by NMR, exhibits features similar to those observed in NC complexes with HIV-1 stem loop RNAs, including the insertion of guanosine nucleobases to hydrophobic clefts on the surface of the zinc fingers and a 3'-to-5' orientation of the RNA relative to protein. Our findings indicate that the previously proposed long-range U5-gag(AUG) interaction is feasible and suggest a potential NC-dependent mechanism for modulating the structure of the 5'-UTR.
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http://dx.doi.org/10.1021/bi8014373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646082PMC
December 2008