Machine learning has been gaining traction in recent years to meet the demand for tools that can efficiently analyze and make sense of the ever-growing databases of biomedical data in health care systems around the world. However, effectively using machine learning methods requires considerable domain expertise, which can be a barrier of entry for bioinformaticians new to computational data science methods. Therefore, off-the-shelf tools that make machine learning more accessible can prove invaluable for bioinformaticians. To this end, we have developed an open source pipeline optimization tool (TPOT-MDR) that uses genetic programming to automatically design machine learning pipelines for bioinformatics studies. In TPOT-MDR, we implement Multifactor Dimensionality Reduction (MDR) as a feature construction method for modeling higher-order feature interactions, and combine it with a new expert knowledge-guided feature selector for large biomedical data sets. We demonstrate TPOT-MDR's capabilities using a combination of simulated and real world data sets from human genetics and find that TPOT-MDR significantly outperforms modern machine learning methods such as logistic regression and eXtreme Gradient Boosting (XGBoost). We further analyze the best pipeline discovered by TPOT-MDR for a real world problem and highlight TPOT-MDR's ability to produce a high-accuracy solution that is also easily interpretable.
@cite_5: Given infinite time, humans would progress through modeling complex data in a manner that is dependent on prior expert knowledge. The goal of the present study is make extensions and enhancements to a computational evolution system (CES) that has the ultimate objective of tinkering with data as a human would. This is accomplished by providing flexibility in the model-building process and a meta-layer that learns how to generate better models. The key to the CES system is the ability to identify and exploit expert knowledge from biological databases or prior analytical results. Our prior results have demonstrated that CES is capable of efficiently navigating these large and rugged fitness landscapes toward the discovery of biologically meaningful genetic models of disease. Further, we have shown that the efficacy of CES is improved dramatically when the system is provided with statistical or biological expert knowledge. The goal of the present study was to apply CES to the genetic analysis of prostate cancer aggressiveness in a large sample of European Americans. We introduce here the use of Pareto-optimization to help address overfitting in the learning system. We further introduce a post-processing step that uses hierarchical cluster analysis to generate expert knowledge from the landscape of best models and their predictions across patients. We find that the combination of Pareto-optimization and post-processing of results greatly improves the genetic analysis of prostate cancer.
@cite_9: Background and objective Detecting complex patterns of association between genetic or environmental risk factors and disease risk has become an important target for epidemiological research. In particular, strategies that provide multifactor interactions or heterogeneous patterns of association can offer new insights into association studies for which traditional analytic tools have had limited success. Materials and methods To concurrently examine these phenomena, previous work has successfully considered the application of learning classifier systems (LCSs), a flexible class of evolutionary algorithms that distributes learned associations over a population of rules. Subsequent work dealt with the inherent problems of knowledge discovery and interpretation within these algorithms, allowing for the characterization of heterogeneous patterns of association. Whereas these previous advancements were evaluated using complex simulation studies, this study applied these collective works to a ‘real-world’ genetic epidemiology study of bladder cancer susceptibility. Results and discussion We replicated the identification of previously characterized factors that modify bladder cancer risk—namely, single nucleotide polymorphisms from a DNA repair gene, and smoking. Furthermore, we identified potentially heterogeneous groups of subjects characterized by distinct patterns of association. Cox proportional hazard models comparing clinical outcome variables between the cases of the two largest groups yielded a significant, meaningful difference in survival time in years (survivorship). A marginally significant difference in recurrence time was also noted. These results support the hypothesis that an LCS approach can offer greater insight into complex patterns of association. Conclusions This methodology appears to be well suited to the dissection of disease heterogeneity, a key component in the advancement of personalized medicine.
Genetic programming and evolutionary computation methods have also been successfully applied to bioinformatics studies, such as @cite_5 @cite_9 , but they do not focus on designing and tuning a series of standard data analysis operations for a specific dataset. As such, although they are related techniques, they do not fall into the automated machine learning domain.