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  1. Article ; Online: Evaluating performance of metagenomic characterization algorithms using in silico datasets generated with FASTQSim

    Darrell O. Ricke;Anna Shcherbina;Nelson Chiu;

    Abstract: BackgroundIn silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics algorithms. Sequenced datasets include background organisms, creating ambiguity in the true source organism for each read. Bacterial and ... ...

    Abstract BackgroundIn silico bacterial, viral, and human truth datasets were generated to evaluate available metagenomics algorithms. Sequenced datasets include background organisms, creating ambiguity in the true source organism for each read. Bacterial and viral datasets were created with even and staggered coverage to evaluate organism identification, read mapping, and gene identification capabilities of available algorithms. These truth datasets are provided as a resource for the development and refinement of metagenomic algorithms. Algorithm performance on these truth datasets can inform decision makers on strengths and weaknesses of available algorithms and how the results may be best leveraged for bacterial and viral organism identification and characterization.\n\nSource organisms were selected to mirror communities described in the Human Microbiome Project as well as the emerging pathogens listed by the National Institute of Allergy and Infectious Diseases. The six in silico datasets were used to evaluate the performance of six leading metagenomics algorithms: MetaScope, Kraken, LMAT, MetaPhlAn, MetaCV, and MetaPhyler.\n\nResultsAlgorithms were evaluated on runtime, true positive organisms identified to the genus and species levels, false positive organisms identified to genus and species level, read mapping, relative abundance estimation, and gene calling. No algorithm out performed the others in all categories, and the algorithm or algorithms of choice strongly depends on analysis goals. MetaPhlAn excels for bacteria and LMAT for viruses. The algorithms were ranked by overall performance using a normalized weighted sum of the above metrics, and MetaScope emerged as the overall winner, followed by Kraken and LMAT.\n\nConclusionsSimulated FASTQ datasets with well-characterized truth data about microbial community composition reveal numerous insights about the relative strengths and weaknesses of the metagenomics algorithms evaluated. The simulated datasets are available to download from the Sequence Read Archive (SRP062063).
    Keywords covid19
    Publisher biorxiv
    Document type Article ; Online
    DOI 10.1101/046532
    Database COVID19

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  2. Article ; Online: Ex vivo observation of granulocyte activity during thrombus formation

    Daria S. Morozova / Alexey A. Martyanov / Sergei I. Obydennyi / Julia-Jessica D. Korobkin / Alexey V. Sokolov / Ekaterina V. Shamova / Irina V. Gorudko / Anna L. Khoreva / Anna Shcherbina / Mikhail A. Panteleev / Anastasia N. Sveshnikova

    BMC Biology, Vol 20, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Abstract Background The process of thrombus formation is thought to involve interactions between platelets and leukocytes. Leukocyte incorporation into growing thrombi has been well established in vivo, and a number of properties of platelet-leukocyte ... ...

    Abstract Abstract Background The process of thrombus formation is thought to involve interactions between platelets and leukocytes. Leukocyte incorporation into growing thrombi has been well established in vivo, and a number of properties of platelet-leukocyte interactions critical for thrombus formation have been characterized in vitro in thromboinflammatory settings and have clinical relevance. Leukocyte activity can be impaired in distinct hereditary and acquired disorders of immunological nature, among which is Wiskott-Aldrich Syndrome (WAS). However, a more quantitative characterization of leukocyte behavior in thromboinflammatory conditions has been hampered by lack of approaches for its study ex vivo. Here, we aimed to develop an ex vivo model of thromboinflammation, and compared granulocyte behavior of WAS patients and healthy donors. Results Thrombus formation in anticoagulated whole blood from healthy volunteers and patients was visualized by fluorescent microscopy in parallel-plate flow chambers with fibrillar collagen type I coverslips. Moving granulocytes were observed in hirudinated or sodium citrate-recalcified blood under low wall shear rate conditions (100 s−1). These cells crawled around thrombi in a step-wise manner with an average velocity of 90–120 nm/s. Pre-incubation of blood with granulocyte priming agents lead to a significant decrease in mean-velocity of the cells and increase in the number of adherent cells. The leukocytes from patients with WAS demonstrated a 1.5-fold lower mean velocity, in line with their impaired actin polymerization. It is noteworthy that in an experimental setting where patients’ platelets were replaced with healthy donor’s platelets the granulocytes’ crawling velocity did not change, thus proving that WASP (WAS protein) deficiency causes disruption of granulocytes’ behavior. Thereby, the observed features of granulocytes crawling are consistent with the neutrophil chemotaxis phenomenon. As most of the crawling granulocytes carried procoagulant platelets teared from thrombi, we propose that the role of granulocytes in thrombus formation is that of platelet scavengers. Conclusions We have developed an ex vivo experimental model applicable for observation of granulocyte activity in thrombus formation. Using the proposed setting, we observed a reduction of motility of granulocytes of patients with WAS. We suggest that our ex vivo approach should be useful both for basic and for clinical research.
    Keywords Thromboinflammation ; Platelets ; Granulocytes ; Chemotaxis ; Flow chambers ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Hematopoietic stem cell transplantation in a patient with type 1 mosaic variegated aneuploidy syndrome

    Alexandra Laberko / Dmitry Balashov / Elena Deripapa / Olga Soldatkina / Elena Raikina / Alexei Maschan / Galina Novichkova / Anna Shcherbina

    Orphanet Journal of Rare Diseases, Vol 14, Iss 1, Pp 1-

    2019  Volume 5

    Abstract: Abstract Background Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. Type 1 MVA (MVA1) is caused by mutations in the budding uninhibited by ... ...

    Abstract Abstract Background Mosaic variegated aneuploidy (MVA) syndrome is a chromosomal instability disorder that leads to aneuploidies of different chromosomes in various tissues. Type 1 MVA (MVA1) is caused by mutations in the budding uninhibited by benzimidazoles 1 homolog beta (BUB1B) gene. The main clinical features of MVA1 syndrome are growth and mental retardation, central nervous system anomalies, microcephaly, and predisposition to cancers. There have been no reports of hematopoietic stem cell transplantation (HSCT) in MVA patients. Results We report an 11-year old boy diagnosed with MVA1 syndrome. The BUB1B gene mutations c.498_505delAAACTTTA and c.1288 + 5G > A were detected using the next generation sequencing (NGS) method. The patient presented with cytopenia soon after birth, but remained stable until 9 years of age, when he developed myelodysplastic syndrome associated with monosomy of chromosome 7. Due to severe dependence on blood transfusions, a TCRαβ+/CD19+ depleted HSCT was performed from a matched unrelated donor (MUD) using a treosulfan-based reduced intensity conditioning (RIC) regimen. The engraftment occurred, and no severe toxicity was observed soon after the HSCT, but on day + 47, graft rejection was detected. It was followed by prolonged pancytopenia and sepsis with multi-organ Enterococcus faecium infection, which led to the patient’s death on day + 156 after HSCT. Conclusions In conclusion, we demonstrate that RIC HSCT with TCRαβ+/CD19+ depletion was well tolerated and resulted in complete hematologic recovery in our MVA1 patient, but, unfortunately, it was followed by rapid graft rejection. This fact needs to be taken into consideration for HSCT in other MVA patients.
    Keywords Mosaic variegated aneuploidy syndrome ; BUB1B gene ; Hematopoietic stem cell transplantation ; TCRαβ+/CD19+ graft depletion ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2019-05-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis

    Xin Liu / Tao Sun / Anna Shcherbina / Qin Li / Inga Jarmoskaite / Kalli Kappel / Gokul Ramaswami / Rhiju Das / Anshul Kundaje / Jin Billy Li

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 17

    Abstract: The RNA sequence and secondary structure regulate RNA editing by ADAR. Here the authors employ a CRISPR/Cas9-mediated saturation mutagenesis and machine learning to predict RNA editing efficiency of specific substrates. ...

    Abstract The RNA sequence and secondary structure regulate RNA editing by ADAR. Here the authors employ a CRISPR/Cas9-mediated saturation mutagenesis and machine learning to predict RNA editing efficiency of specific substrates.
    Keywords Science ; Q
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Biological Insights Into Muscular Strength

    Emmi Tikkanen / Stefan Gustafsson / David Amar / Anna Shcherbina / Daryl Waggott / Euan A. Ashley / Erik Ingelsson

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    Genetic Findings in the UK Biobank

    2018  Volume 9

    Abstract: Abstract We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our ... ...

    Abstract Abstract We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength (P <5 × 10−8). Of these, 64 were associated (P < 0.01 and consistent direction) also in the replication dataset (N = 111,610). eQTL analyses highlighted several genes known to play a role in neuro-developmental disorders or brain function, and the results from meta-analysis showed a significant enrichment of gene expression of brain-related transcripts. Further, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents’ age of death and education. We also showed that grip strength had shared biological pathways with indicators of frailty, including cognitive performance scores. By use of Mendelian randomization, we provide evidence that higher grip strength is protective of both coronary heart disease (OR = 0.69, 95% CI 0.60–0.79, P < 0.0001) and atrial fibrillation (OR = 0.75, 95% CI 0.62–0.90, P = 0.003). In conclusion, our results show shared genetic aetiology between grip strength, and cardiometabolic and cognitive health; and suggest that maintaining muscular strength could prevent future cardiovascular events.
    Keywords Medicine ; R ; Science ; Q
    Subject code 300
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis

    Anna Shcherbina / Jacqueline Larouche / Paula Fraczek / Benjamin A. Yang / Lemuel A. Brown / James F. Markworth / Carolina H. Chung / Mehwish Khaliq / Kanishka de Silva / Jeongmoon J. Choi / Mohammad Fallahi-Sichani / Sriram Chandrasekaran / Young C. Jang / Susan V. Brooks / Carlos A. Aguilar

    Cell Reports, Vol 32, Iss 4, Pp 107964- (2020)

    2020  

    Abstract: Summary: During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [ ...

    Abstract Summary: During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue-resident stem cells called satellite cells (or muscle stem cells [MuSCs]), but in aging, MuSCs decrease in numbers and regenerative capacity. The transcriptional networks and epigenetic changes that confer diminished regenerative function in MuSCs as a result of natural aging are only partially understood. Herein, we use an integrative genomics approach to profile MuSCs from young and aged animals before and after injury. Integration of these datasets reveals aging impacts multiple regulatory changes through significant differences in gene expression, metabolic flux, chromatin accessibility, and patterns of transcription factor (TF) binding activities. Collectively, these datasets facilitate a deeper understanding of the regulation tissue-resident stem cells use during aging and healing.
    Keywords regeneration ; heterochromatin ; expression ; vitamin A ; 1-carbon metabolism ; MyoD ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation

    Andrea Accogli / Saurabh Shakya / Taewoo Yang / Christine Insinna / Soo Yeon Kim / David Bell / Kirill R. Butov / Mariasavina Severino / Marcello Niceta / Marcello Scala / Hyun Sik Lee / Taekyeong Yoo / Jimmy Stauffer / Huijie Zhao / Chiara Fiorillo / Marina Pedemonte / Maria C. Diana / Simona Baldassari / Viktoria Zakharova /
    Anna Shcherbina / Yulia Rodina / Christina Fagerberg / Laura Sønderberg Roos / Jolanta Wierzba / Artur Dobosz / Amanda Gerard / Lorraine Potocki / Jill A. Rosenfeld / Seema R. Lalani / Tiana M. Scott / Daryl Scott / Mahshid S. Azamian / Raymond Louie / Hannah W. Moore / Neena L. Champaigne / Grace Hollingsworth / Annalaura Torella / Vincenzo Nigro / Rafal Ploski / Vincenzo Salpietro / Federico Zara / Simone Pizzi / Giovanni Chillemi / Marzia Ognibene / Erin Cooney / Jenny Do / Anders Linnemann / Martin J. Larsen / Suzanne Specht / Kylie J. Walters / Hee-Jung Choi / Murim Choi / Marco Tartaglia / Phillippe Youkharibache / Jong-Hee Chae / Valeria Capra / Sung-Gyoo Park / Christopher J. Westlake

    Nature Communications, Vol 15, Iss 1, Pp 1-

    2024  Volume 20

    Abstract: Abstract WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ... ...

    Abstract Abstract WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.
    Keywords Science ; Q
    Subject code 572
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Human inherited complete STAT2 deficiency underlies inflammatory viral diseases

    Giorgia Bucciol / Leen Moens / Masato Ogishi / Darawan Rinchai / Daniela Matuozzo / Mana Momenilandi / Nacim Kerrouche / Catherine M. Cale / Elsa R. Treffeisen / Mohammad Al Salamah / Bandar K. Al-Saud / Alain Lachaux / Remi Duclaux-Loras / Marie Meignien / Aziz Bousfiha / Ibtihal Benhsaien / Anna Shcherbina / Anna Roppelt / COVID Human Genetic Effort /
    Florian Gothe / Nadhira Houhou-Fidouh / Scott J. Hackett / Lisa M. Bartnikas / Michelle C. Maciag / Mohammed F. Alosaimi / Janet Chou / Reem W. Mohammed / Bishara J. Freij / Emmanuelle Jouanguy / Shen-Ying Zhang / Stephanie Boisson-Dupuis / Vivien Béziat / Qian Zhang / Christopher J.A. Duncan / Sophie Hambleton / Jean-Laurent Casanova / Isabelle Meyts

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Volume 12

    Abstract: STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells ... ...

    Abstract STAT2 is a transcription factor activated by type I and III IFNs. We report 23 patients with loss-of-function variants causing autosomal recessive (AR) complete STAT2 deficiency. Both cells transfected with mutant STAT2 alleles and the patients’ cells displayed impaired expression of IFN-stimulated genes and impaired control of in vitro viral infections. Clinical manifestations from early childhood onward included severe adverse reaction to live attenuated viral vaccines (LAV) and severe viral infections, particularly critical influenza pneumonia, critical COVID-19 pneumonia, and herpes simplex virus type 1 (HSV-1) encephalitis. The patients displayed various types of hyperinflammation, often triggered by viral infection or after LAV administration, which probably attested to unresolved viral infection in the absence of STAT2-dependent types I and III IFN immunity. Transcriptomic analysis revealed that circulating monocytes, neutrophils, and CD8+ memory T cells contributed to this inflammation. Several patients died from viral infection or heart failure during a febrile illness with no identified etiology. Notably, the highest mortality occurred during early childhood. These findings show that AR complete STAT2 deficiency underlay severe viral diseases and substantially impacts survival.
    Keywords Immunology ; Medicine ; R
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Physical activity, sleep and cardiovascular health data for 50,000 individuals from the MyHeart Counts Study

    Steven G. Hershman / Brian M. Bot / Anna Shcherbina / Megan Doerr / Yasbanoo Moayedi / Aleksandra Pavlovic / Daryl Waggott / Mildred K. Cho / Mary E. Rosenberger / William L. Haskell / Jonathan Myers / Mary Ann Champagne / Emmanuel Mignot / Dario Salvi / Martin Landray / Lionel Tarassenko / Robert A. Harrington / Alan C. Yeung / Michael V. McConnell /
    Euan A. Ashley

    Scientific Data, Vol 6, Iss 1, Pp 1-

    2019  Volume 10

    Abstract: Design Type(s)observation design · source-based data analysis objective · data collection and processing objectiveMeasurement Type(s)physical activity · sleepTechnology Type(s)crowd-sourced data generationFactor Type(s)sex · height · weight · age · ... ...

    Abstract Design Type(s)observation design · source-based data analysis objective · data collection and processing objectiveMeasurement Type(s)physical activity · sleepTechnology Type(s)crowd-sourced data generationFactor Type(s)sex · height · weight · age · smoking status measurement · employment statusSample Characteristic(s)Homo sapiens · United States of America Machine-accessible metadata file describing the reported data (ISA-Tab format)
    Keywords Science ; Q
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: The effect of digital physical activity interventions on daily step count

    Anna Shcherbina, MS / Steven G Hershman, PhD / Laura Lazzeroni, ProfPhD / Abby C King, ProfPhD / Jack W O'Sullivan, MBBS / Eric Hekler, PhD / Yasbanoo Moayedi, MD / Aleksandra Pavlovic, BS / Daryl Waggott, MSc / Abhinav Sharma, MD / Alan Yeung, MD / Jeffrey W Christle, PhD / Matthew T Wheeler, MD / Michael V McConnell, MD / Robert A Harrington, ProfMD / Euan A Ashley, ProfMBChB

    The Lancet: Digital Health, Vol 1, Iss 7, Pp e344-e

    a randomised controlled crossover substudy of the MyHeart Counts Cardiovascular Health Study

    2019  Volume 352

    Abstract: Summary: Background: Smartphone apps might enable interventions to increase physical activity, but few randomised trials testing this hypothesis have been done. The MyHeart Counts Cardiovascular Health Study is a longitudinal smartphone-based study with ... ...

    Abstract Summary: Background: Smartphone apps might enable interventions to increase physical activity, but few randomised trials testing this hypothesis have been done. The MyHeart Counts Cardiovascular Health Study is a longitudinal smartphone-based study with the aim of elucidating the determinants of cardiovascular health. We aimed to investigate the effect of four different physical activity coaching interventions on daily step count in a substudy of the MyHeart Counts Study. Methods: In this randomised, controlled crossover trial, we recruited adults (aged ≥18 years) in the USA with access to an iPhone smartphone (Apple, Cupertino, CA, USA; version 5S or newer) who had downloaded the MyHeart Counts app (version 2.0). After completion of a 1 week baseline period of interaction with the MyHeart Counts app, participants were randomly assigned to receive one of 24 permutations (four combinations of four 7 day interventions) in a crossover design using a random number generator built into the app. Interventions consisted of either daily prompts to complete 10 000 steps, hourly prompts to stand following 1 h of sitting, instructions to read the guidelines from the American Heart Association website, or e-coaching based upon the individual's personal activity patterns from the baseline week of data collection. Participants completed the trial in a free-living setting. Due to the nature of the interventions, participants could not be masked from the intervention. Investigators were not masked to intervention allocation. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in the modified intention-to-treat analysis set, which included all participants who had completed 7 days of baseline monitoring and at least 1 day of one of the four interventions. This trial is registered with ClinicalTrials.gov, NCT03090321. Findings: Between Dec 12, 2016, and June 6, 2018, 2783 participants consented to enrol in the coaching study, of whom 1075 completed 7 days of baseline ...
    Keywords Computer applications to medicine. Medical informatics ; R858-859.7
    Subject code 796
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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