Population-based analysis of ocular<i>Chlamydia trachomatis</i>in trachoma-endemic West African communities identifies genomic markers of disease severity

Pickering, Harry; Coll, Francesc Español i; Phelan, Jody; Burr, Sarah E.; Cassama, Eunice; Nabicassa, Meno; Seth-Smith, Helena M. B.; Hadfield, James; Cutliffe, Leslie T.; Clarke, Ian N.; Mabey, David; Bailey, Robin L.; Clark, Taane G.; Thomson, Nicholas R.; Holland, Martin J.

doi:10.1101/205336

Cited by 3 publications

(5 citation statements)

References 112 publications

(137 reference statements)

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“…Recently, a novel software package, LocTree3 [26], which integrates SVM with a homology algorithm, has been proposed to perform SLP on proteins from all domains of life, including Archaea, Bacteria, and Eukaryota. LocTree3 has been used in a number of recently published papers [27–29]. However, a recent study suggests that the performance of specifically developed machine learning tools shows no significant improvement over that of homology-search-based methods [30], which is consistent with what we demonstrate in this paper.…”

Section: Introductionsupporting

confidence: 90%

A high-precision hybrid algorithm for predicting eukaryotic protein subcellular localization

Zhang

Huang

et al. 2019

Preprint

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21 Motivation 22 Subcellular location plays an essential role in protein synthesis, transport, and secretion, thus it is an 23 important step in understanding the mechanisms of trait-related proteins. Generally, homology methods provide 24 reliable homology-based results with small E-values. We must resort to pattern recognition algorithms (SVM, 25 Fisher discriminant, KNN, random forest, etc.) for proteins that do not share significant homologous domains 26 with known proteins. However, satisfying results are seldom obtained. 27 Results 28 Here, a novel hybrid method "Basic Local Alignment Search Tool+Smith-Waterman+Needleman-Wunsch" 29 or BLAST+SWNW, has been obtained by integrating a loosened E-value Basic Local Alignment Search Tool 30 (BLAST) with the Smith-Waterman (SW) and Needleman-Wunsch (NW) algorithms, and this method has been 31 introduced to predict protein subcellular localization in eukaryotes. When tested on Dataset I and Dataset II, 32 BLAST+SWNW showed an average accuracy of 97.18% and 99.60%, respectively, surpassing the performance 33 of other algorithms in predicting eukaryotic protein subcellular localization. 34 Availability and Implementation 35 BLAST+SWNW is an open source collaborative initiative available in the GitHub repository 36 (https://github.com/ZHANGDAHAN/BLAST-SWNW-for-SLP or http://202.206.64.158:80/link/72016CAC 37 26E4298B3B7E0EAF42288935 ) 38 Contact 39

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Section: Introductionsupporting

confidence: 90%

A high-precision hybrid algorithm for predicting eukaryotic protein subcellular localization

Zhang

Huang

et al. 2019

Preprint

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“…trachomatis enrichment from rectal samples 53 . This RNA bait methodology has therefore been used to understand genomic diversity in circulating C. trachomatis ocular, urogenital and LGV lineages from clinical specimens but with varying success [53][54][55][56][57] .…”

Section: Introductionmentioning

confidence: 99%

Whole-Genome Enrichment and Sequencing ofChlamydia trachomatisDirectly from Patient Clinical Vaginal and Rectal Swabs

Bowden

Joseph

Cartee

et al. 2020

Preprint

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Chlamydia trachomatis is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. U.S. cases have been steadily increasing for more than a decade in both the urogenital tract and rectum. C. trachomatis is an obligate intracellular bacterium that is not easily cultured, limiting the capacity for genome studies to understand strain diversity and emergence among various patient populations globally. While Agilent SureSelectXT target-enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival and rectal samples, efficiencies are only 60-80% for >95-100% genome coverage. We therefore re-designed and expanded the RNA bait library to augment enrichment of the organism from clinical samples to improve efficiency. We describe the expanded library, the limit of detection for C. trachomatis genome copy input, and the 100% efficiency and high-resolution of generated genomes where genomic recombination among paired vaginal and rectal specimens from four patients was identified. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, among geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.

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“…In the sub-study comparing resolution achieved between WGS, ompA and MLST in a set of 71 WGS from Bijagos Islands, Guinea-Bissau [31], MLST discriminatory index was higher for the samples in this study compared with the Guinea-Bissau population (D = 0.825 vs D = 0.743), neither had discriminatory power considered to be necessary for molecular epidemiology (D = 0.95). Minimum spanning tree (MST) analyses showed minimal sharing of STs between these studies; however, STs from these studies did form overlapping clusters (Fig.…”

Section: One-year Impact Of Mda On Organism Loadmentioning

confidence: 60%

“…MST and phylogenetic analyses also identified considerable discrepancy in the relatedness of isolates between WGS and MLST. WGS of C. trachomatis is possible directly from clinical samples with as few as 500 genome copies [31,[82][83][84]. However, it is still relatively expensive compared to MLST.…”

Section: Discussionmentioning

confidence: 99%

“…For the sub-study evaluating the resolution achieved between MLST and WGS variation, complete ompA typing, WGS and MLST were compared in a population from the Bijagos Islands, Guinea-Bissau. A set of 71 WGS from the Bijagos Islands [31], with inferred MLST and ompA types, was utilised to compare these three approaches and their utility in epidemiological studies.…”

Section: Sequence Typingmentioning

confidence: 99%

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Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal

et al. 2019

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Background: Mass drug administration (MDA) with azithromycin is a cornerstone of the trachoma elimination strategy. Although the global prevalence of active trachoma has declined considerably, prevalence persists or even increases in some communities and districts. To increase understanding of MDA impact, we investigated the prevalence of active trachoma and ocular C. trachomatis prevalence, organism load, and circulating strains at baseline and one-year post-MDA in The Gambia and Senegal. Methods: Pre-and one-year post-MDA, children aged 0-9 years were examined for clinical signs of trachoma in six Gambian and 12 Senegalese villages. Ocular swabs from each child's right conjunctiva were tested for evidence of ocular C. trachomatis infection and organism load (ompA copy number), and ompA and multi-locus sequence typing (MLST) was performed. Results: A total of 1171 children were examined at baseline and follow-up in The Gambia. Active trachoma prevalence decreased from 23.9% to 17.7%, whereas ocular C. trachomatis prevalence increased from 3.0% to 3.8%. In Senegal, 1613 and 1771 children were examined at baseline and follow-up, respectively. Active trachoma prevalence decreased from 14.9% to 8.0%, whereas ocular C. trachomatis prevalence increased from 1.8% to 3.6%. Higher organism load was associated with having active trachoma and severe inflammation. Sequence typing demonstrated that all Senegalese samples were genovar A, whereas Gambian samples were a mix of genovars A and B. MLST provided evidence of clustering at village and household levels and demonstrated differences of strain variant frequencies in Senegal, indicative of an "outbreak". MLST, including partial ompA typing, provided greater discriminatory power than complete ompA typing. Conclusions: We found that one round of MDA led to an overall decline in active trachoma prevalence but no impact on ocular C. trachomatis infection, with heterogeneity observed between villages studied. This could not be explained by MDA coverage or number of different circulating strains pre-and post-MDA. The poor correlation between active trachoma and infection prevalence supports the need for further work on alternative indicators to

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Population-based analysis of ocularChlamydia trachomatisin trachoma-endemic West African communities identifies genomic markers of disease severity

Cited by 3 publications

References 112 publications

A high-precision hybrid algorithm for predicting eukaryotic protein subcellular localization

A high-precision hybrid algorithm for predicting eukaryotic protein subcellular localization

Whole-Genome Enrichment and Sequencing ofChlamydia trachomatisDirectly from Patient Clinical Vaginal and Rectal Swabs

Impact of a single round of mass drug administration with azithromycin on active trachoma and ocular Chlamydia trachomatis prevalence and circulating strains in The Gambia and Senegal

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