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      Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response

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          Abstract

          There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1β and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

          Abstract

          Gaining mechanistic insight into the microbiological and immunological factors that are associated with spontaneous preterm birth is important for the development of prevention strategies. Here authors show that the complement system in conjunction with specific vaginal microbial and associated immunological changes are contributing to this condition.

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            DADA2: High resolution sample inference from Illumina amplicon data

            We present DADA2, a software package that models and corrects Illumina-sequenced amplicon errors. DADA2 infers sample sequences exactly, without coarse-graining into OTUs, and resolves differences of as little as one nucleotide. In several mock communities DADA2 identified more real variants and output fewer spurious sequences than other methods. We applied DADA2 to vaginal samples from a cohort of pregnant women, revealing a diversity of previously undetected Lactobacillus crispatus variants.
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              Cutadapt removes adapter sequences from high-throughput sequencing reads

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                Author and article information

                Contributors
                l.sykes@imperial.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                21 February 2022
                21 February 2022
                2022
                : 13
                : 975
                Affiliations
                [1 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion and Reproduction, , Imperial College London, ; London, UK
                [2 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, March of Dimes Prematurity Research Center at Imperial College London, ; London, UK
                [3 ]GRID grid.417895.6, ISNI 0000 0001 0693 2181, St. Mary’s Hospital, , Imperial College Healthcare NHS Trust, ; London, UK
                [4 ]GRID grid.83440.3b, ISNI 0000000121901201, Elizabeth Garrett Anderson Institute for Women’s Health, , University College London, ; London, UK
                [5 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, University of Edinburgh Usher Institute, ; Edinburgh, UK
                [6 ]GRID grid.5337.2, ISNI 0000 0004 1936 7603, Faculty of Health Sciences, , University of Bristol, ; Bristol, UK
                [7 ]GRID grid.417895.6, ISNI 0000 0001 0693 2181, Chelsea & Westminster Hospital, , Imperial College Healthcare NHS Trust, ; London, UK
                [8 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Infectious Diseases, , Imperial College London, ; London, UK
                [9 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Immunology and Inflammation, , Imperial College London, ; London, UK
                Author information
                http://orcid.org/0000-0002-6253-4919
                http://orcid.org/0000-0002-0199-6140
                http://orcid.org/0000-0003-4308-856X
                http://orcid.org/0000-0002-7579-4947
                http://orcid.org/0000-0002-1458-3791
                http://orcid.org/0000-0002-4186-5567
                http://orcid.org/0000-0002-7806-5707
                Article
                28620
                10.1038/s41467-022-28620-1
                8861006
                35190561
                db0de30d-cb74-455b-b4b4-cb3391c7ee9c
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 March 2021
                : 28 January 2022
                Funding
                Funded by: The March of Dimes
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                microbial communities,mucosal immunology,reproductive signs and symptoms,predictive markers

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