Using a targeted molecular knockdown approach to interrogate the causal molecular underpinnings of EGFR-persistent activation, we found that lapatinib-resistant cells were no longer oncogene addicted to HER2-HER3-PI3K seenaling, as seen in the parental lapatinib-sensitive cell lines, but instead were dependent on a heregulin (HRG -driven HRG -drivenI3K-PDK1 signaling axis.
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This would bias the power comparison as one method would have the causal SNP directly interrogated, while the other method would have to rely on LD to detect the association.
While complete re-sequencing of GWAS regions in large sample sets would ultimately be desirable, our approach undoubtedly represents the most time and cost-effective method available at the present time to interrogate and prioritize the most plausible causal variants underpinning GWAS studies.
To provide further evidence that this indel in ALG2 was the causal mutation, exome data were interrogated in their entirety, rather than with restriction to the candidate interval on chromosome 9 (Supplementary material).
Two-sample, two-step MR can be utilized to interrogate tissue-specific DNA methylation as a potential causal intermediate phenotype.
Indeed, the likely influence of antiandrogenic chemicals on each of the measured responses is clearly demonstrated using a modeling strategy that allows for the effects of steroidal estrogens first before interrogating the data for the existence of additional causal factors.
RCR interrogates the experimental data against a knowledgebase of possible causal relationships for all of the context-specific nodes and edges in the literature model to identify upstream controllers of the mRNA state changes (gene-expression changes) observed in the data set.
In the case of RNA expression data, Causal Network Modeling employs an automated reverse causal analysis approach which interrogates the mouse knowledge assembly model to identify upstream controllers for the RNA state changes observed in the experiment.
The advent of high-throughput technologies that can rapidly interrogate whole genomes, epigenomes and proteomes, has also revolutionized our ability to detect genetic variants that might be causal for a number of sleep disorders.
