PubMed HealthSearch

Biomedical subjects

Emmanuelle Waubant

Publications and source records attributed to Emmanuelle Waubant.

2 recordsLinked to original sources

Proportionality-based association metrics in count compositional data.

Compositional data comprise vectors that describe the constituent parts of a whole. Data arising from various -omics platforms such as 16S and RNA sequencing are compositional in nature. In this kind of data, correlations between features on raw counts have no meaningful interpretation. Metrics of proportionality were formulated to address this problem. However, an inherent bias arises when these metrics are calculated empirically on count-based measures due to variability in read depths. We quantify the bias introduced by empirically calculating proportionality-based association metrics in count data. Additionally, we propose a means of estimating these metrics within a logit-normal multinomial model in pursuit of more accurate estimates. The model-based estimates are shown to outperform empirical estimates in simulated data and are applied to a mouse embryonic stem cell single-cell sequencing dataset, as well as a pediatric-onset multiple sclerosis metagenomic dataset.

Animals

Rare and low-frequency coding genetic variants contribute to pediatric-onset multiple sclerosis.

BACKGROUND: Rare genetic variants are emerging as important contributors to the heritability of multiple sclerosis (MS). Whether rare variants also contribute to pediatric-onset multiple sclerosis (POMS) is unknown. OBJECTIVE: To test whether genes harboring rare variants associated with adult-onset MS risk (PRF1, PRKRA, NLRP8, and HDAC7) and 52 major histocompatibility complex (MHC) genes are associated with POMS. METHODS: We analyzed DNA samples from 330 POMS cases and 306 controls from the US Network of Pediatric MS Centers and Kaiser Permanente Northern California for which Illumina ExomeChip genotypes were available. Using the gene-based method "SKAT-O," we tested the association between candidate genes and POMS risk. RESULTS: After correction for multiple comparisons, one adult-onset MS gene (PRF1, p = 2.70 × 10-3) and two MHC genes (BRD2, p = 5.89 × 10-5 and AGER, p = 7.96 × 10-5) were significantly associated with POMS. Results suggest these are independent of HLA-DRB1*1501. CONCLUSION: Findings support a role for rare coding variants in POMS susceptibility. In particular, rare minor alleles within PRF1 were more common among individuals with POMS compared to controls while the opposite was true for rare variants within significant MHC genes, BRD2 and AGER. These genes would not have been identified by common variant studies, emphasizing the merits of investigating rare genetic variation in complex diseases.

Child