Abstract | Here, we adapt an established meta-analysis framework to address the problem of drug repurposing using an ensemble of disease signatures. |
Abstract | Our meta-analysis pipeline is general, and applicable to any disease context; it can be applied to improve the results of signature-based drug repurposing by leveraging the large number of disease signatures in the public domain. |
Author Summary | Here, we design a meta-analysis pipeline that takes in a large set of disease signatures and then identifies drugs that consistently reverse deleterious gene changes. |
Author Summary | We show that our meta-analysis pipeline increases the reproducibility of top drug hits, and then extensively characterize new lung cancer drug candidates in silico. |
CMapBatch meta-analysis strategy: From individual cancer gene signatures to candidate therapeutics | CMapBatch meta-analysis strategy: From individual cancer gene signatures to candidate therapeutics |
CMapBatch meta-analysis strategy: From individual cancer gene signatures to candidate therapeutics | Our CMapBatch meta-analysis pipeline comprises the following steps (Fig. |
Candidate therapeutics | CMapBatch meta-analysis pipeline. |
Introduction | Next, we apply meta-analysis to identify which drugs are consistently ranked as the best candidates across all disease signatures. |
Introduction | Thus, we perform the meta-analysis at a later step: our method combines lists of drugs rather than lists of genes. |
Introduction | First, we conducted a meta-analysis using CMapBatch to identify drugs that reverse the transcriptional changes seen with lung cancer across 21 gene signatures (see Table 1). |
Meta-analysis | Meta-analysis |
A signalling entropy derived prognostic score outperforms microarray based prognostic indicators in lung adenocarcinoma | CADMI expression performed comparably to the SE score in a meta-analysis , however, it was outperformed by pathological tumour stage (CADMI expression vs stage: p = 0.03). |
A signalling entropy derived prognostic score outperforms microarray based prognostic indicators in lung adenocarcinoma | We found that the SE score improved over stage Ia/b alone in a meta-analysis across 765 stage I lung ade-nocarcinomas (SE score+stage vs stage: p = 0.025), whereas CADMI expression made no improvement over stage Ia/b (CADMI expression+stage vs stage: p = 0.13, Fig. |
Signalling entropy is prognostic in stage I lung adenocarcinoma | Sub-staging by size is currently the standard clinical approach to stratify stage I tumours, however, on meta-analysis we found that this stratification, unlike signalling entropy was not significantly prognostic over the stage I stratum (Fig. |
Signalling entropy is prognostic in the major subtypes of breast cancer | Meta-analysis revealed that signalling entropy is prognostic across both ER positive and ER negative samples (ER positive: c-indeX = 0.63, 95% CI = (0.604, 0.657),p = 8.5e — 15, ER negative: c-indeX = 0.57, 95% CI = (0.538, 0.602), p = 0.032, Fig. |
Signalling entropy is prognostic in the major subtypes of breast cancer | In a meta-analysis over the 10 breast cancer validation sets we found that unlike signalling entropy Mam-maPrint was not significantly prognostic over ER negative samples (Fig. |
Supporting Information | Meta-analysis comparison of signalling entropy with OncotypeDX. |
Supporting Information | The overall concordance indices were derived via meta-analysis using a random effects model. |
Supporting Information | Meta-analysis across 10 data sets reveals that signalling entropy performs comparably to OncotypeDX across (A) ER positive samples and (B) ER negative samples. |
Author Summary | In this meta-analysis across 148 studies, we ask whether it is possible to identify patterns that differentiate five emotion categories—fear, anger, disgust, sadness, and happiness—in a way that is consistent across studies. |
Bayesian Spatial Point Processes (BSPP) for Neuroimaging Meta-Analysis | Bayesian Spatial Point Processes (BSPP) for Neuroimaging Meta-Analysis |
Bayesian Spatial Point Processes (BSPP) for Neuroimaging Meta-Analysis | The BSPP is built on a hierarchical marked independent cluster process designed for functional neuroimaging meta-analysis [38]. |
Introduction | Meta-analysis is uniquely suited to addressing our two questions because it examines findings from many studies and laboratories that utilize different procedures, stimuli, and samples. |
The Bayesian Spatial Point Process (BSPP) Model | The BSPP model differs from standard univariate [12,13,39] and co-activation based [40,41] approaches to meta-analysis in several fundamental ways. |
Abstract | We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis . |
Abstract | We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. |
Data for the validation of the prediction model | Where multiple studies on nasopharyngeal carriage were conducted within different subsets of the same population that were monitored for IPD, the results from those studies were combined via a Bayesian random effects meta-analysis . |
Results | Respective studies were pooled through Bayesian random effects meta-analysis to provide a single estimate of the proportion of VT among carriers for each setting (Table 1 and $2 Fig). |
Statistical analysis | Where the proportion of VT carriers was derived through the Bayesian meta-analysis we drew the bootstrap samples from the respective posterior distribution instead (S2 Fig). |