# Deep neural network improves the estimation of polygenic risk scores for breast cancer

arXiv: https://arxiv.org/abs/2307.13010 · HTML: https://mlsanity.com/paper/2307.13010/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 57 references that are in the map.
- First posted on arXiv 24 Jul 2023.

## Builds on (most cited first, 7 of 7)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Batch Normalization: Accelerating Deep Network Training by Reducing Internal Covariate Shift](https://mlsanity.com/paper/1502.03167/) (2015)
- ["Why Should I Trust You?": Explaining the Predictions of Any Classifier](https://mlsanity.com/paper/1602.04938/) (2016)
- [Learning Important Features Through Propagating Activation Differences](https://mlsanity.com/paper/1704.02685/) (2017)
- [Deep Learning in Neural Networks: An Overview](https://mlsanity.com/paper/1404.7828/) (2014)
- [Empirical Evaluation of Rectified Activations in Convolutional Network](https://mlsanity.com/paper/1505.00853/) (2015)
- [Utilising Deep Learning and Genome Wide Association Studies for Epistatic-Driven Preterm Birth Classification in African-American Women](https://mlsanity.com/paper/1801.02977/) (2018)

## Abstract (arXiv)

Polygenic risk scores (PRS) estimate the genetic risk of an individual for a complex disease based on many genetic variants across the whole genome. In this study, we compared a series of computational models for estimation of breast cancer PRS. A deep neural network (DNN) was found to outperform alternative machine learning techniques and established statistical algorithms, including BLUP, BayesA and LDpred. In the test cohort with 50% prevalence, the Area Under the receiver operating characteristic Curve (AUC) were 67.4% for DNN, 64.2% for BLUP, 64.5% for BayesA, and 62.4% for LDpred. BLUP, BayesA, and LPpred all generated PRS that followed a normal distribution in the case population. However, the PRS generated by DNN in the case population followed a bi-modal distribution composed of two normal distributions with distinctly different means. This suggests that DNN was able to separate the case population into a high-genetic-risk case sub-population with an average PRS significantly higher than the control population and a normal-genetic-risk case sub-population with an average PRS similar to the control population. This allowed DNN to achieve 18.8% recall at 90% precision in the test cohort with 50% prevalence, which can be extrapolated to 65.4% recall at 20% precision in a general population with 12% prevalence. Interpretation of the DNN model identified salient variants that were assigned insignificant p-values by association studies, but were important for DNN prediction. These variants may be associated with the phenotype through non-linear relationships.