Biology subjects

Lees, J.

Publications and source records attributed to Lees, J..

3 recordsLinked to original sources

bioRxiv2018

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, and identified variants in CCDC33 associated with susceptibility. Pneumococcal variation explained a large amount of invasive potential, but serotype explained only half of this variation. Newly developed methods identified pneumococcal genes involved in invasiveness including pspC and zmpD, and allowed a human-bacteria interaction analysis, finding associations between pneumococcal lineage and STK32C.

genomics↗

bioRxiv2018

Protein structure and function analyses to understand the implication of mutually exclusive splicing

Alternative splicing (AS) has been suggested as one of the major processes expanding the diversity of proteomes in multicellular organisms. Mutually exclusive exons (MXE) provide one form of AS that is less likely to disrupt protein structure and is over-represented in the proteome compared to other forms of AS. We used domain structure information from the CATH classification to perform a systematic structural analysis of the effects of MXE splicing in high quality animal genomes (e.g. human, fly, mouse and 2 fishes) and we were able to annotate approximately 50% of MXE events with structural information. For those MXE events which can be mapped to a structure, we found that although embedded in domains, they were strongly enriched in surface exposed residues. We also demonstrated that the variable residues between splicing events lie close to known and/or predicted functional sites. We present some examples of MXE events in proteins that have important roles in cells. This work presents the first large scale systematic study of the structural/functional effects of MXE splicing using predominantly domain based modelling and functional annotation tools. Our study supports and expands on previous work in this field and helps to build a picture of how MXE events facilitate evolution of new functions.

bioinformatics↗

bioRxiv2018

pyseer: a comprehensive tool for microbial pangenome-wide association studies

SummaryGenome-wide association studies (GWAS) in microbes face different challenges to eukaryotes and have been addressed by a number of different methods. pyseer brings these techniques together in one package tailored to microbial GWAS, allows greater flexibility of the input data used, and adds new methods to interpret the association results.\n\nAvailability and Implementationpyseer is written in python and is freely available at https://github.com/mgalardini/pyseer, or can be installed through pip. Documentation and a tutorial are available at http://pyseer.readthedocs.io.\n\nContactjohn.lees@nyumc.org and marco@ebi.ac.uk\n\nSupplementary informationSupplementary data are available online.

bioinformatics↗