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Chandler, C. E.

Publications and source records attributed to Chandler, C. E..

2 recordsLinked to original sources

Enhanced longitudinal differential expression detection in proteomics with robust reproducibility optimization regression

Quantitative proteomics has matured into an established tool and longitudinal proteomic experiments have begun to emerge. However, no effective, simple-to-use differential expression method for longitudinal proteomics data has been released. Typically, such data is noisy, contains missing values, has only few time points and biological replicates. To address this need, we provide a comprehensive evaluation of several existing differential expression methods for high-throughput longitudinal omics data and introduce a new method, Robust longitudinal Differential Expression (RolDE). The methods were evaluated using nearly 2000 semi-simulated spike-in proteomic datasets and a large experimental dataset. The RolDE method performed overall best; it was most tolerant to missing values, displayed good reproducibility and was the top method in ranking the results in a biologically meaningful way. Furthermore, contrary to many approaches, the open source RolDE does not require prior knowledge concerning the types of differences searched, but can easily be applied even by non-experienced users.

bioinformatics

Host Adaptation Predisposes Pseudomonas aeruginosa to Type VI Secretion System-Mediated Predation by the Burkholderia cepacia Complex

Pseudomonas aeruginosa (Pa) and Burkholderia cepacia complex (Bcc) species are opportunistic lung pathogens of individuals with cystic fibrosis (CF). While Pa can initiate long-term infections in younger CF patients, Bcc infections only arise in teenagers and adults. Both Pa and Bcc use type VI secretion systems (T6SS) to mediate interbacterial competition. Here, we show that Pa isolates from teenage/adult CF patients, but not those from young CF patients, are outcompeted by the epidemic Bcc isolate Burkholderia cenocepacia strain AU1054 (BcAU1054) in a T6SS-dependent manner. The genomes of susceptible Pa isolates harbor T6SS-abrogating mutations, the repair of which, in some cases, rendered the isolates resistant. Moreover, seven of eight Bcc strains outcompeted Pa strains isolated from the same patients. Our findings suggest that certain mutations that arise as Pa adapts to the CF lung abrogate T6SS activity, making Pa and its human host susceptible to potentially fatal Bcc superinfection.

microbiology