Hash-Based Core Genome Multilocus Sequence Typing for Clostridium difficile.
23 December 2019
Eyre DW, Peto TEA, Crook DW, Walker AS, Wilcox MH.
Journal of Clinical Microbiology, (2019) pg 1-11
Pathogen whole-genome sequencing has huge potential as a tool to better understand infection transmission. However, rapidly identifying closely related genomes among a background of thousands of other genomes is challenging. Here, we describe a refinement to core genome multilocus sequence typing (cgMLST) in which alleles at each gene are reproducibly converted to a unique hash, or short string of letters (hash-cgMLST). This avoids the resource-intensive need for a single centralized database of sequentially numbered alleles. We test the reproducibility and discriminatory power of cgMLST/hash-cgMLST compared to those of mapping-based approaches in Clostridium difficile, using repeated sequencing of the same isolates (replicates) and data from consecutive infection isolates from six English hospitals. Hash-cgMLST provided the same results as standard cgMLST, with minimal performance penalty. Comparing 272 replicate sequence pairs using reference-based mapping, there were 0, 1, or 2 single-nucleotide polymorphisms (SNPs) between 262 (96%), 5 (2%), and 1 (<1%) of the pairs, respectively. Using hash-cgMLST, 218 (80%) of replicate pairs assembled with SPAdes had zero gene differences, and 31 (11%), 5 (2%), and 18 (7%) pairs had 1, 2, and >2 differences, respectively. False gene differences were clustered in specific genes and associated with fragmented assemblies, but were reduced using the SKESA assembler. Considering 412 pairs of infections with ≤2 SNPS, i.e., consistent with recent transmission, 376 (91%) had ≤2 gene differences and 16 (4%) had ≥4. Comparing a genome to 100,000 others took <1 min using hash-cgMLST. Hash-cgMLST is an effective surveillance tool for rapidly identifying clusters of related genomes. However, cgMLST/hash-cgMLST generate more false variants than mapping-based approaches. Follow-up mapping-based analyses are likely required to precisely define close genetic relationships.
Antenatal exposure to solar radiation and learning disabilities: Population cohort study of 422,512 children
8 July 2019
Hastie CE, Mackay DF, Clemens TL, Cherrie MPC, King A, Dibben C, Pell JP Scientific Reports (2019) 9(9356):1-9 Learning disability varies by month of conception. The underlying mechanism is...
Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres
21 November 2019
Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah AD, Channon KM, Weber JN, Thursz MR, Elliott P, Hemingway H, Williams B, Asselbergs F, O’Sullivan M, Kharbanda R, Lord...