LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 71

Search options

  1. Article ; Online: Benchmarking Metagenomics Tools for Taxonomic Classification.

    Ye, Simon H / Siddle, Katherine J / Park, Daniel J / Sabeti, Pardis C

    Cell

    2019  Volume 178, Issue 4, Page(s) 779–794

    Abstract: Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the ... ...

    Abstract Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.
    MeSH term(s) Bacteria/classification ; Bacteria/genetics ; Benchmarking/methods ; Databases, Genetic ; Fungi/classification ; Fungi/genetics ; Metagenome/genetics ; Metagenomics/methods ; Phylogeny ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Software ; Viruses/classification ; Viruses/genetics
    Language English
    Publishing date 2019-08-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.07.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article: Population variation in miRNAs and isomiRs and their impact on human immunity to infection

    Rotival, Maxime / Siddle, Katherine J / Silvert, Martin / Pothlichet, Julien / Quach, Hélène / Quintana-Murci, Lluis

    Genome biology. 2020 Dec., v. 21, no. 1

    2020  

    Abstract: BACKGROUND: MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized. RESULTS: We generate 977 miRNA-sequencing profiles from ... ...

    Abstract BACKGROUND: MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized. RESULTS: We generate 977 miRNA-sequencing profiles from primary monocytes from individuals of African and European ancestry following activation of three TLR pathways (TLR4, TLR1/2, and TLR7/8) or infection with influenza A virus. We find that immune activation leads to important modifications in the miRNA and isomiR repertoire, particularly in response to viral challenges. These changes are much weaker than those observed for protein-coding genes, suggesting stronger selective constraints on the miRNA response to stimulation. This is supported by the limited genetic control of miRNA expression variability (miR-QTLs) and the lower occurrence of gene-environment interactions, in stark contrast with eQTLs that are largely context-dependent. We also detect marked differences in miRNA expression between populations, which are mostly driven by non-genetic factors. On average, miR-QTLs explain approximately 60% of population differences in expression of their cognate miRNAs and, in some cases, evolve adaptively, as shown in Europeans for a miRNA-rich cluster on chromosome 14. Finally, integrating miRNA and mRNA data from the same individuals, we provide evidence that the canonical model of miRNA-driven transcript degradation has a minor impact on miRNA-mRNA correlations, which are, in our setting, mainly driven by co-transcription. CONCLUSION: Together, our results shed new light onto the factors driving miRNA and isomiR diversity at the population level and constitute a useful resource for evaluating their role in host differences of immunity to infection.
    Keywords Europeans ; Influenza A virus ; Toll-like receptor 1 ; Toll-like receptor 4 ; Toll-like receptor 7 ; ancestry ; chromosomes ; genes ; genotype-environment interaction ; immune response ; messenger RNA ; microRNA ; models ; monocytes ; sequence analysis ; transcription (genetics)
    Language English
    Dates of publication 2020-12
    Size p. 187.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6906
    ISSN (online) 1474-760X
    ISSN 1465-6906
    DOI 10.1186/s13059-020-02098-w
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  3. Article ; Online: High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection.

    Normandin, Erica / Rudy, Melissa / Barkas, Nikolaos / Schaffner, Stephen F / Levine, Zoe / Padera, Robert F / Babadi, Mehrtash / Mukerji, Shibani S / Park, Daniel J / MacInnis, Bronwyn L / Siddle, Katherine J / Sabeti, Pardis C / Solomon, Isaac H

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 574

    Abstract: SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic ... ...

    Abstract SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects. The majority of the 180 viral variants identified within subjects are unique to individual tissue samples. We find more high-frequency (>10%) minor variants in subjects with a longer disease course, with one subject harboring ten such variants, exclusively in extrapulmonary tissues. One tissue-specific high-frequency variant was a nonsynonymous mutation in the furin-cleavage site of the spike protein. Our findings suggest adaptation and/or compartmentalized infection, illuminating the basis of extrapulmonary COVID-19 symptoms and potential for viral reservoirs, and have broad utility for investigating human pathogens.
    MeSH term(s) Humans ; COVID-19 ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Mutation ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2023-02-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-34256-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Neuropathological features of SARS-CoV-2 delta and omicron variants.

    Normandin, Erica / Valizadeh, Navid / Rudmann, Emily A / Uddin, Rockib / Dobbins, Sabrina T / MacInnis, Bronwyn L / Padera, Robert F / Siddle, Katherine J / Lemieux, Jacob E / Sabeti, Pardis C / Mukerji, Shibani S / Solomon, Isaac H

    Journal of neuropathology and experimental neurology

    2023  Volume 82, Issue 4, Page(s) 283–295

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continually evolving resulting in variants with increased transmissibility, more severe disease, reduced effectiveness of treatments or vaccines, or diagnostic detection failure. The SARS- ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continually evolving resulting in variants with increased transmissibility, more severe disease, reduced effectiveness of treatments or vaccines, or diagnostic detection failure. The SARS-CoV-2 Delta variant (B.1.617.2 and AY lineages) was the dominant circulating strain in the United States from July to mid-December 2021, followed by the Omicron variant (B.1.1.529 and BA lineages). Coronavirus disease 2019 (COVID-19) has been associated with neurological sequelae including loss of taste/smell, headache, encephalopathy, and stroke, yet little is known about the impact of viral strain on neuropathogenesis. Detailed postmortem brain evaluations were performed for 22 patients from Massachusetts, including 12 who died following infection with Delta variant and 5 with Omicron variant, compared to 5 patients who died earlier in the pandemic. Diffuse hypoxic injury, occasional microinfarcts and hemorrhage, perivascular fibrinogen, and rare lymphocytes were observed across the 3 groups. SARS-CoV-2 protein and RNA were not detected in any brain samples by immunohistochemistry, in situ hybridization, or real-time quantitative PCR. These results, although preliminary, demonstrate that, among a subset of severely ill patients, similar neuropathological features are present in Delta, Omicron, and non-Delta/non-Omicron variant patients, suggesting that SARS-CoV-2 variants are likely to affect the brain by common neuropathogenic mechanisms.
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Neuropathology ; Stroke
    Language English
    Publishing date 2023-02-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nlad015
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Population variation in miRNAs and isomiRs and their impact on human immunity to infection.

    Rotival, Maxime / Siddle, Katherine J / Silvert, Martin / Pothlichet, Julien / Quach, Hélène / Quintana-Murci, Lluis

    Genome biology

    2020  Volume 21, Issue 1, Page(s) 187

    Abstract: Background: MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized.: Results: We generate 977 miRNA-sequencing profiles ... ...

    Abstract Background: MicroRNAs (miRNAs) are key regulators of the immune system, yet their variation and contribution to intra- and inter-population differences in immune responses is poorly characterized.
    Results: We generate 977 miRNA-sequencing profiles from primary monocytes from individuals of African and European ancestry following activation of three TLR pathways (TLR4, TLR1/2, and TLR7/8) or infection with influenza A virus. We find that immune activation leads to important modifications in the miRNA and isomiR repertoire, particularly in response to viral challenges. These changes are much weaker than those observed for protein-coding genes, suggesting stronger selective constraints on the miRNA response to stimulation. This is supported by the limited genetic control of miRNA expression variability (miR-QTLs) and the lower occurrence of gene-environment interactions, in stark contrast with eQTLs that are largely context-dependent. We also detect marked differences in miRNA expression between populations, which are mostly driven by non-genetic factors. On average, miR-QTLs explain approximately 60% of population differences in expression of their cognate miRNAs and, in some cases, evolve adaptively, as shown in Europeans for a miRNA-rich cluster on chromosome 14. Finally, integrating miRNA and mRNA data from the same individuals, we provide evidence that the canonical model of miRNA-driven transcript degradation has a minor impact on miRNA-mRNA correlations, which are, in our setting, mainly driven by co-transcription.
    Conclusion: Together, our results shed new light onto the factors driving miRNA and isomiR diversity at the population level and constitute a useful resource for evaluating their role in host differences of immunity to infection.
    MeSH term(s) Black People ; Genome, Human ; Humans ; Immunity ; Infections/immunology ; Infections/metabolism ; MicroRNAs/immunology ; MicroRNAs/metabolism ; Monocytes/metabolism ; Quantitative Trait Loci ; RNA Isoforms/immunology ; RNA Isoforms/metabolism ; White People
    Chemical Substances MicroRNAs ; RNA Isoforms
    Language English
    Publishing date 2020-07-30
    Publishing country England
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-020-02098-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article: Benchmarking Metagenomics Tools for Taxonomic Classification

    Ye, Simon H / Siddle, Katherine J / Park, Daniel J / Sabeti, Pardis C

    Cell. 2019 Aug. 08, v. 178, no. 4

    2019  

    Abstract: Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the ... ...

    Abstract Metagenomic sequencing is revolutionizing the detection and characterization of microbial species, and a wide variety of software tools are available to perform taxonomic classification of these data. The fast pace of development of these tools and the complexity of metagenomic data make it important that researchers are able to benchmark their performance. Here, we review current approaches for metagenomic analysis and evaluate the performance of 20 metagenomic classifiers using simulated and experimental datasets. We describe the key metrics used to assess performance, offer a framework for the comparison of additional classifiers, and discuss the future of metagenomic data analysis.
    Keywords computer software ; data collection ; metagenomics
    Language English
    Dates of publication 2019-0808
    Size p. 779-794.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2019.07.010
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

  7. Article ; Online: Investigating the etiologies of non-malarial febrile illness in Senegal using metagenomic sequencing.

    Levine, Zoë C / Sene, Aita / Mkandawire, Winnie / Deme, Awa B / Ndiaye, Tolla / Sy, Mouhamad / Gaye, Amy / Diedhiou, Younouss / Mbaye, Amadou M / Ndiaye, Ibrahima M / Gomis, Jules / Ndiop, Médoune / Sene, Doudou / Faye Paye, Marietou / MacInnis, Bronwyn L / Schaffner, Stephen F / Park, Daniel J / Badiane, Aida S / Colubri, Andres /
    Ndiaye, Mouhamadou / Sy, Ngayo / Sabeti, Pardis C / Ndiaye, Daouda / Siddle, Katherine J

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 747

    Abstract: The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical ... ...

    Abstract The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata in a cross-sectional study of febrile patients and healthy controls in a low malaria burden area. Using 16S and untargeted sequencing, we detected viral, bacterial, or eukaryotic pathogens in 23% (38/163) of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15.5% and 3.8% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model that can distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs (F1 score: 0.823). These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.
    MeSH term(s) Humans ; Senegal/epidemiology ; Cross-Sectional Studies ; Malaria/diagnosis ; Malaria/epidemiology ; Plasmodium ; Fever/epidemiology ; Borrelia/genetics
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-44800-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Single-cell profiling of lncRNA expression during Ebola virus infection in rhesus macaques.

    Santus, Luisa / Sopena-Rios, Maria / García-Pérez, Raquel / Lin, Aaron E / Adams, Gordon C / Barnes, Kayla G / Siddle, Katherine J / Wohl, Shirlee / Reverter, Ferran / Rinn, John L / Bennett, Richard S / Hensley, Lisa E / Sabeti, Pardis C / Melé, Marta

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3866

    Abstract: Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and are pivotal mediators of the immune response, yet little is known about their properties at the single-cell level. Here, we generate a multi-tissue bulk RNAseq dataset from ... ...

    Abstract Long non-coding RNAs (lncRNAs) are involved in numerous biological processes and are pivotal mediators of the immune response, yet little is known about their properties at the single-cell level. Here, we generate a multi-tissue bulk RNAseq dataset from Ebola virus (EBOV) infected and not-infected rhesus macaques and identified 3979 novel lncRNAs. To profile lncRNA expression dynamics in immune circulating single-cells during EBOV infection, we design a metric, Upsilon, to estimate cell-type specificity. Our analysis reveals that lncRNAs are expressed in fewer cells than protein-coding genes, but they are not expressed at lower levels nor are they more cell-type specific when expressed in the same number of cells. In addition, we observe that lncRNAs exhibit similar changes in expression patterns to those of protein-coding genes during EBOV infection, and are often co-expressed with known immune regulators. A few lncRNAs change expression specifically upon EBOV entry in the cell. This study sheds light on the differential features of lncRNAs and protein-coding genes and paves the way for future single-cell lncRNA studies.
    MeSH term(s) Animals ; Hemorrhagic Fever, Ebola/genetics ; RNA, Long Noncoding/genetics ; Macaca mulatta ; Ebolavirus/genetics ; Virus Internalization
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2023-06-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-39627-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: The Red Queen's long race: human adaptation to pathogen pressure.

    Siddle, Katherine J / Quintana-Murci, Lluis

    Current opinion in genetics & development

    2014  Volume 29, Page(s) 31–38

    Abstract: Pathogens, and the infectious diseases they cause, have been paramount among the threats encountered by humans in their expansions throughout the globe. Numerous studies have identified immunity and host defence genes as being among the functions most ... ...

    Abstract Pathogens, and the infectious diseases they cause, have been paramount among the threats encountered by humans in their expansions throughout the globe. Numerous studies have identified immunity and host defence genes as being among the functions most strongly targeted by selection, most likely pathogen-driven. The dissection of the form and intensity of such selective pressures have increased our knowledge of the biological relevance of the underlying immunological mechanisms in host defence. Although the identities of the specific infectious agents imposing these selective pressures remain, in most cases, elusive, the impact of several pathogens, notably malaria and cholera, has been described. However, past selection against infectious diseases may have some fitness costs upon environmental changes, potentially leading to maladaptation and immunopathology.
    MeSH term(s) Adaptation, Physiological/genetics ; Adaptive Immunity/genetics ; Disease Resistance/genetics ; Environment ; Evolution, Molecular ; Genetic Fitness/genetics ; Host-Pathogen Interactions/genetics ; Humans ; Models, Genetic ; Selection, Genetic
    Language English
    Publishing date 2014-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2014.07.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article: Negative Selection by Spiral Inertial Microfluidics Improves Viral Recovery and Sequencing from Blood

    Choi, Kyungyong / Ryu, Hyunryul / Siddle, Katherine J / Piantadosi, Anne / Freimark, Lisa / Park, Daniel J / Sabeti, Pardis / Han, Jongyoon

    Analytical chemistry. 2018 Mar. 14, v. 90, no. 7

    2018  

    Abstract: In blood samples from patients with viral infection, it is often important to separate viral particles from human cells, for example, to minimize background in performing viral whole genome sequencing. Here, we present a microfluidic device that uses ... ...

    Abstract In blood samples from patients with viral infection, it is often important to separate viral particles from human cells, for example, to minimize background in performing viral whole genome sequencing. Here, we present a microfluidic device that uses spiral inertial microfluidics with continuous circulation to separate host cells from viral particles and free nucleic acid. We demonstrate that this device effectively reduces white blood cells, red blood cells, and platelets from both whole blood and plasma samples with excellent recovery of viral nucleic acid. Furthermore, microfluidic separation leads to greater viral genome coverage and depth, highlighting an important application of this device in processing clinical samples for viral genome sequencing.
    Keywords blood platelets ; blood sampling ; erythrocytes ; genome ; humans ; leukocytes ; nucleic acids ; patients ; sequence analysis ; virion
    Language English
    Dates of publication 2018-0314
    Size p. 4657-4662.
    Publishing place American Chemical Society
    Document type Article
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.7b05200
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

To top