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https://www.selleckchem.com/products/avitinib-ac0010.html tastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence. Gene-set analyses measure the association between a disease of interest and a "set" of genes related to a biological pathway. These analyses often incorporate gene network properties to account for differential contributions of each gene. We extend this concept further-defining gene contributions based on biophysical properties-by leveraging mathematical models of biology to predict the effects of genetic perturbations on a particular downstream function. We present a method that combines gene weights from model predictions and gene ranks from genome-wide association studies into a weighted gene-set test. We demonstrate in simulation how such a method can improve statistical power. To this effect, we identify a gene set, weighted by model-predicted contributions to intracellular calcium ion concentration, that is significantly related to bipolar disorder in a small dataset (P = 0.04; n = 544). We reproduce this finding using publicly available summary data from the Psychiatric Genomics Consortium (P = 1.7 × 10-4; n = 41,653). By contrast, an approach using a general calcium signaling pathway did not detect a significant association with bipolar dis

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