TY - JOUR
T1 - Explainable discovery of disease biomarkers
T2 - The case of ovarian cancer to illustrate the best practice in machine learning and Shapley analysis
AU - Huang, Weitong
AU - Suominen, Hanna
AU - Liu, Tommy
AU - Rice, Gregory
AU - Salomon, Carlos
AU - Barnard, Amanda S.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/5
Y1 - 2023/5
N2 - Objective: Ovarian cancer is a significant health issue with lasting impacts on the community. Despite recent advances in surgical, chemotherapeutic and radiotherapeutic interventions, they have had only marginal impacts due to an inability to identify biomarkers at an early stage. Biomarker discovery is challenging, yet essential for improving drug discovery and clinical care. Machine learning (ML) techniques are invaluable for recognising complex patterns in biomarkers compared to conventional methods, yet they can lack physical insights into diagnosis. eXplainable Artificial Intelligence (XAI) is capable of providing deeper insights into the decision-making of complex ML algorithms increasing their applicability. We aim to introduce best practice for combining ML and XAI techniques for biomarker validation tasks. Methods: We focused on classification tasks and a game theoretic approach based on Shapley values to build and evaluate models and visualise results. We described the workflow and apply the pipeline in a case study using the CDAS PLCO Ovarian Biomarkers dataset to demonstrate the potential for accuracy and utility. Results: The case study results demonstrate the efficacy of the ML pipeline, its consistency, and advantages compared to conventional statistical approaches. Conclusion: The resulting guidelines provide a general framework for practical application of XAI in medical research that can inform clinicians and validate and explain cancer biomarkers.
AB - Objective: Ovarian cancer is a significant health issue with lasting impacts on the community. Despite recent advances in surgical, chemotherapeutic and radiotherapeutic interventions, they have had only marginal impacts due to an inability to identify biomarkers at an early stage. Biomarker discovery is challenging, yet essential for improving drug discovery and clinical care. Machine learning (ML) techniques are invaluable for recognising complex patterns in biomarkers compared to conventional methods, yet they can lack physical insights into diagnosis. eXplainable Artificial Intelligence (XAI) is capable of providing deeper insights into the decision-making of complex ML algorithms increasing their applicability. We aim to introduce best practice for combining ML and XAI techniques for biomarker validation tasks. Methods: We focused on classification tasks and a game theoretic approach based on Shapley values to build and evaluate models and visualise results. We described the workflow and apply the pipeline in a case study using the CDAS PLCO Ovarian Biomarkers dataset to demonstrate the potential for accuracy and utility. Results: The case study results demonstrate the efficacy of the ML pipeline, its consistency, and advantages compared to conventional statistical approaches. Conclusion: The resulting guidelines provide a general framework for practical application of XAI in medical research that can inform clinicians and validate and explain cancer biomarkers.
KW - Cancer screening
KW - Evaluation study as topic
KW - Medical informatics
KW - Supervised machine learning
UR - http://www.scopus.com/inward/record.url?scp=85153078314&partnerID=8YFLogxK
U2 - 10.1016/j.jbi.2023.104365
DO - 10.1016/j.jbi.2023.104365
M3 - Article
SN - 1532-0464
VL - 141
SP - 1
EP - 9
JO - Journal of Biomedical Informatics
JF - Journal of Biomedical Informatics
M1 - 104365
ER -