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This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes.
Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
DrDimont: explainable drug response prediction from differential analysis of multi-omics networks
(2022)
Motivation:
While it has been well established that drugs affect and help patients differently, personalized drug response predictions remain challenging.
Solutions based on single omics measurements have been proposed, and networks provide means to incorporate molecular interactions into reasoning.
However, how to integrate the wealth of information contained in multiple omics layers still poses a complex problem.
Results:
We present DrDimont, Drug response prediction from Differential analysis of multi-omics networks.
It allows for comparative conclusions between two conditions and translates them into differential drug response predictions.
DrDimont focuses on molecular interactions.
It establishes condition-specific networks from correlation within an omics layer that are then reduced and combined into heterogeneous, multi-omics molecular networks. A novel semi-local, path-based integration step ensures integrative conclusions. Differential predictions are derived from comparing the condition-specific integrated networks.
DrDimont's predictions are explainable, i.e. molecular differences that are the source of high differential drug scores can be retrieved. We predict differential drug response in breast cancer using transcriptomics, proteomics, phosphosite and metabolomics measurements and contrast estrogen receptor positive and receptor negative patients. DrDimont performs better than drug prediction based on differential protein expression or PageRank when evaluating it on ground truth data from cancer cell lines. We find proteomic and phosphosite layers to carry most information for distinguishing drug response.