Publications

Next-generation sequencing (NGS) approaches rapidly produce millions to billions of short reads, which allow pathogen detection and discovery in human clinical, animal and environmental samples. A major limitation of sequence homology-based identification for highly divergent microorganisms is the short length of reads generated by most highly parallel sequencing technologies. Short reads require a high level of sequence similarities to annotated genes to confidently predict gene function or homology. Such recognition of highly divergent homologues can be improved by reference-free (de novo) assembly of short overlapping sequence reads into larger contigs. We describe an ensemble strategy that integrates the sequential use of various de Bruijn graph and overlap-layout-consensus assemblers with a novel partitioned sub-assembly approach. We also proposed new quality metrics that are suitable for evaluating metagenome de novo assembly. We demonstrate that this new ensemble strategy tested using in silico spike-in, clinical and environmental NGS datasets achieved significantly better contigs than current approaches.

The association between sexual violence and depression is well known, but the temporal aspects of the association have not been well established. We analyzed data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed every 3 months for a median of 1.8 years of follow-up. The method of generalized estimating equations (GEE) was used to model the marginal expectation of depression symptom severity (Hopkins Symptom Checklist for Depression), mental health-related quality of life (MOS-HIV Mental Health Summary), and heavy drinking (Alcohol Use Disorders Identification Test) as a function of self-reported forced-sex victimization in the 3 months prior to interview. Estimates were adjusted for variables known to confound the association between victimization and mental health status. To assess any potential reciprocal relationships, we reversed the temporal ordering of the exposures and outcomes and refitted similar GEE models. In multivariable analyses, victimization was associated with greater depression symptom severity (b = 0.17; 95% CI = [0.02, 0.33]) and lower mental health-related quality of life (b = -5.65; 95% CI = [-9.34, -1.96]), as well as increased risks for probable depression (adjusted relative risk [ARR] = 1.58; 95% CI = [1.01, 2.49) and heavy drinking (ARR = 3.99; 95% CI = [1.84, 8.63]). We did not find strong evidence of a reciprocal relationship. Our findings suggest that forced sex is associated with adverse mental health outcomes among HIV-positive women in rural Uganda. Given the substantial mental health-related impacts of victimization, effective health sector responses are needed.