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Phylogenetic profiling: how much input data is enough?

ABSTRACT: Phylogenetic profiling is a well-established approach for predicting gene function based on patterns of gene presence and absence across species. Much of the recent developments have focused on methodological improvements, but relatively little is known about the effect of input data size on the quality of predictions. In this work, we ask: how many genomes and functional annotations need to be considered for phylogenetic profiling to be effective? Phylogenetic profiling generally benefits from an increased amount of input data. However, by decomposing this improvement in predictive accuracy in terms of the contribution of additional genomes and of additional annotations, we observed diminishing returns in adding more than ? 100 genomes, whereas increasing the number of annotations remained strongly beneficial throughout. We also observed that maximising phylogenetic diversity within a clade of interest improves predictive accuracy, but the effect is small compared to changes in the number of genomes under comparison. Finally, we show that these findings are supported in light of the Open World Assumption, which posits that functional annotation databases are inherently incomplete. All the tools and data used in this work are available for reuse from http://lab.dessimoz.org/14_phylprof. Scripts used to analyse the data are available on request from the authors.

SUBMITTER: Skunca N

PROVIDER: S-EPMC4332489 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Phylogenetic profiling: how much input data is enough?

Škunca Nives N Dessimoz Christophe C

PloS one 20150213 2

Phylogenetic profiling is a well-established approach for predicting gene function based on patterns of gene presence and absence across species. Much of the recent developments have focused on methodological improvements, but relatively little is known about the effect of input data size on the quality of predictions. In this work, we ask: how many genomes and functional annotations need to be considered for phylogenetic profiling to be effective? Phylogenetic profiling generally benefits from ...[more]

PMID: 25679783

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Project description:PurposeThe mechanisms by which depressive symptoms negatively affect clinical outcomes in patients with coronary artery disease (CAD) remain poorly understood. Previous interventions that have attempted to treat depressive symptoms in patients with CAD to improve their clinical outcomes have been disappointing. Our objectives were, among a cohort of CAD patients, to evaluate the impact of depressive symptoms over time, controlling for comorbidity, in determining both successful long-term lifestyle change (ie, increased physical activity), and cardiovascular morbidity and mortality outcomes. In addition, we examined the impact of physical activity changes over time on 2 known mediators of cardiovascular morbidity: parasympathetic tone and inflammation.MethodsClinical data were previously collected (2004-2006) from 242 elective/urgent coronary angioplasty patients who participated in a prospective randomized controlled trial evaluating the efficacy of a behavioral intervention versus an educational control to motivate physical activity over 12 months. Exclusion criteria included: (1) inability to walk; (2) enrollment in other risk-reduction trials; (3) non-English speaking; and (4) lack of cardiologist's permission to increase physical activity. Participants were assessed every 2 months for interval clinical events and physical activity. In addition, biomarkers were collected at baseline and at 12 months in a subset of 54 participants; these biomarkers included low-frequency heart rate variability (lfHRV), high-frequency heart rate variability (hfHRV), serum C-reactive protein, interleukin-6, and salivary cortisol.FindingsThe mean age of participants was 63 years and 30% were female. Overall, 37% had high depressive symptoms at baseline. Patients with high depressive symptoms who achieved an increase in physical activity of ≥336 kilocalories(kcal)/week by 12 months had significantly lower rates of cardiovascular morbidity/mortality (5.1% vs. 21.3%; odds ratio [OR], 0.20, [95% CI, 0.04-0.98]; P = 0.03). In a multivariate model examining cardiovascular morbidity/mortality in patients with high depressive symptoms, an increase in physical activity of ≥336 kcal/week reduced the risk of new cardiovascular morbidity/mortality (OR, 0.11 [95% CI, 0.02-0.81]; P < 0.03), and comorbidity increased the risk (OR, 1.58 [95% CI, 1.18-2.13]; P = 0.002). In a generalized structural equation model, increasing physical activity by ≥336 kcal/week decreased the risk of complications, and comorbidity increased the risk. Furthermore, increasing physical activity (≥336 kcal/week) predicted an increase in hfHRV, a marker of parasympathetic tone, and the increase in hfHRV predicted a reduction in the proinflammatory mediators interleukin-6 and C-reactive protein.ImplicationsThis study found a threshold in physical activity in CAD patients with depressive symptoms that is associated with a decrease in cardiovascular morbidity and mortality. Exercise maintenance at this level may improve clinical outcomes via enhanced parasympathetic tone and decreased inflammation. ClinicalTrials.gov identifier: NCT00248846.

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Phylogenetic profiling: how much input data is enough?

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Phylogenetic profiling: how much input data is enough?

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