Explainable clinical decision support system: opening black-box meta-learner algorithm expert's based

Mathematical optimization methods are the basic mathematical tools of all artificial intelligence theory. In the field of machine learning and deep learning the examples with which algorithms learn (training data) are used by sophisticated cost functions which can have solutions in closed form or through approximations. The interpretability of the models used and the relative transparency, opposed to the opacity of the black-boxes, is related to how the algorithm learns and this occurs through the optimization and minimization of the errors that the machine makes in the learning process. In particular in the present work is introduced a new method for the determination of the weights in an ensemble model, supervised and unsupervised, based on the well known Analytic Hierarchy Process method (AHP). This method is based on the concept that behind the choice of different and possible algorithms to be used in a machine learning problem, there is an expert who controls the decisionmaking process. The expert assigns a complexity score to each algorithm (based on the concept of complexity-interpretability trade-off) through which the weight with which each model contributes to the training and prediction phase is determined. In addition, different methods are presented to evaluate the performance of these algorithms and explain how each feature in the model contributes to the prediction of the outputs. The interpretability techniques used in machine learning are also combined with the method introduced based on AHP in the context of clinical decision support systems in order to make the algorithms (black-box) and the results interpretable and explainable, so that clinical-decision-makers can take controlled decisions together with the concept of "right to explanation" introduced by the legislator, because the decision-makers have a civil and legal responsibility of their choices in the clinical field based on systems that make use of artificial intelligence. No less, the central point is the interaction between the expert who controls the algorithm construction process and the domain expert, in this case the clinical one. Three applications on real data are implemented with the methods known in the literature and with those proposed in this work: one application concerns cervical cancer, another the problem related to diabetes and the last one focuses on a specific pathology developed by HIV-infected individuals. All applications are supported by plots, tables and explanations of the results, implemented through Python libraries. The main case study of this thesis regarding HIV-infected individuals concerns an unsupervised ensemble-type problem, in which a series of clustering algorithms are used on a set of features and which in turn produce an output used again as a set of meta-features to provide a set of labels for each given cluster. The meta-features and labels obtained by choosing the best algorithm are used to train a Logistic regression meta-learner, which in turn is used through some explainability methods to provide the value of the contribution that each algorithm has had in the training phase. The use of Logistic regression as a meta-learner classifier is motivated by the fact that it provides appreciable results and also because of the easy explainability of the estimated coefficients

Deep Neural Networks based Meta-Learning for Network Intrusion Detection

The digitization of different components of industry and inter-connectivity among indigenous networks have increased the risk of network attacks. Designing an intrusion detection system to ensure security of the industrial ecosystem is difficult as network traffic encompasses various attack types, including new and evolving ones with minor changes. The data used to construct a predictive model for computer networks has a skewed class distribution and limited representation of attack types, which differ from real network traffic. These limitations result in dataset shift, negatively impacting the machine learning models' predictive abilities and reducing the detection rate against novel attacks. To address the challenges, we propose a novel deep neural network based Meta-Learning framework; INformation FUsion and Stacking Ensemble (INFUSE) for network intrusion detection. First, a hybrid feature space is created by integrating decision and feature spaces. Five different classifiers are utilized to generate a pool of decision spaces. The feature space is then enriched through a deep sparse autoencoder that learns the semantic relationships between attacks. Finally, the deep Meta-Learner acts as an ensemble combiner to analyze the hybrid feature space and make a final decision. Our evaluation on stringent benchmark datasets and comparison to existing techniques showed the effectiveness of INFUSE with an F-Score of 0.91, Accuracy of 91.6%, and Recall of 0.94 on the Test+ dataset, and an F-Score of 0.91, Accuracy of 85.6%, and Recall of 0.87 on the stringent Test-21 dataset. These promising results indicate the strong generalization capability and the potential to detect network attacks.Comment: Pages: 15, Figures: 10 and Tables:

Machine Learning-Based Models for Prediction of Toxicity Outcomes in Radiotherapy

In order to limit radiotherapy (RT)-related side effects, effective toxicity prediction and assessment schemes are essential. In recent years, the growing interest toward artificial intelligence and machine learning (ML) within the science community has led to the implementation of innovative tools in RT. Several researchers have demonstrated the high performance of ML-based models in predicting toxicity, but the application of these approaches in clinics is still lagging, partly due to their low interpretability. Therefore, an overview of contemporary research is needed in order to familiarize practitioners with common methods and strategies. Here, we present a review of ML-based models for predicting and classifying RT-induced complications from both a methodological and a clinical standpoint, focusing on the type of features considered, the ML methods used, and the main results achieved. Our work overviews published research in multiple cancer sites, including brain, breast, esophagus, gynecological, head and neck, liver, lung, and prostate cancers. The aim is to define the current state of the art and main achievements within the field for both researchers and clinicians

Using Data Mining Techniques to Assess the Impact of COVID-19 on the Auto Insurance Industry in China

Since coronavirus disease 2019 (COVID-19) was discovered at the end of 2019, the whole world has been severely affected. The insurance industry, regarded as an important factor in recovery, has also been affected by COVID-19. However, effective data mining techniques have rarely been utilized in the insurance industry in China, especially under the circumstances of COVID-19. Although some traditional statistical analysis methods have been applied to this area, the limitation of the lack of data distribution still cannot be efficiently overcome. With the machine learning technique proposed in this thesis, this limitation can be solved by using a stacking model with great generalization ability. In this research, the ElasticNet, LightGBM, and Random Forest approaches were employed as base learners; ridge and LASSO regression were used as meta-models to increase the prediction accuracy; and the SHAP value was utilized to explain the impact of COVID-19 on the insurance industry in China. The stacking meta-model in this thesis has a mean absolute percentage error (MAPE) of 12.57134, whereas the average value in the past week is 21.50972, and the MAPE of ElasticNet is 22.57935. In conclusion, COVID-19 affects the auto insurance industry in China

Analysing functional genomics data using novel ensemble, consensus and data fusion techniques

Motivation: A rapid technological development in the biosciences and in computer science in the last decade has enabled the analysis of high-dimensional biological datasets on standard desktop computers. However, in spite of these technical advances, common properties of the new high-throughput experimental data, like small sample sizes in relation to the number of features, high noise levels and outliers, also pose novel challenges. Ensemble and consensus machine learning techniques and data integration methods can alleviate these issues, but often provide overly complex models which lack generalization capability and interpretability. The goal of this thesis was therefore to develop new approaches to combine algorithms and large-scale biological datasets, including novel approaches to integrate analysis types from different domains (e.g. statistics, topological network analysis, machine learning and text mining), to exploit their synergies in a manner that provides compact and interpretable models for inferring new biological knowledge. Main results: The main contributions of the doctoral project are new ensemble, consensus and cross-domain bioinformatics algorithms, and new analysis pipelines combining these techniques within a general framework. This framework is designed to enable the integrative analysis of both large- scale gene and protein expression data (including the tools ArrayMining, Top-scoring pathway pairs and RNAnalyze) and general gene and protein sets (including the tools TopoGSA , EnrichNet and PathExpand), by combining algorithms for different statistical learning tasks (feature selection, classification and clustering) in a modular fashion. Ensemble and consensus analysis techniques employed within the modules are redesigned such that the compactness and interpretability of the resulting models is optimized in addition to the predictive accuracy and robustness. The framework was applied to real-word biomedical problems, with a focus on cancer biology, providing the following main results: (1) The identification of a novel tumour marker gene in collaboration with the Nottingham Queens Medical Centre, facilitating the distinction between two clinically important breast cancer subtypes (framework tool: ArrayMining) (2) The prediction of novel candidate disease genes for Alzheimer’s disease and pancreatic cancer using an integrative analysis of cellular pathway definitions and protein interaction data (framework tool: PathExpand, collaboration with the Spanish National Cancer Centre) (3) The prioritization of associations between disease-related processes and other cellular pathways using a new rule-based classification method integrating gene expression data and pathway definitions (framework tool: Top-scoring pathway pairs) (4) The discovery of topological similarities between differentially expressed genes in cancers and cellular pathway definitions mapped to a molecular interaction network (framework tool: TopoGSA, collaboration with the Spanish National Cancer Centre) In summary, the framework combines the synergies of multiple cross-domain analysis techniques within a single easy-to-use software and has provided new biological insights in a wide variety of practical settings

Analysing functional genomics data using novel ensemble, consensus and data fusion techniques

Motivation: A rapid technological development in the biosciences and in computer science in the last decade has enabled the analysis of high-dimensional biological datasets on standard desktop computers. However, in spite of these technical advances, common properties of the new high-throughput experimental data, like small sample sizes in relation to the number of features, high noise levels and outliers, also pose novel challenges. Ensemble and consensus machine learning techniques and data integration methods can alleviate these issues, but often provide overly complex models which lack generalization capability and interpretability. The goal of this thesis was therefore to develop new approaches to combine algorithms and large-scale biological datasets, including novel approaches to integrate analysis types from different domains (e.g. statistics, topological network analysis, machine learning and text mining), to exploit their synergies in a manner that provides compact and interpretable models for inferring new biological knowledge. Main results: The main contributions of the doctoral project are new ensemble, consensus and cross-domain bioinformatics algorithms, and new analysis pipelines combining these techniques within a general framework. This framework is designed to enable the integrative analysis of both large- scale gene and protein expression data (including the tools ArrayMining, Top-scoring pathway pairs and RNAnalyze) and general gene and protein sets (including the tools TopoGSA , EnrichNet and PathExpand), by combining algorithms for different statistical learning tasks (feature selection, classification and clustering) in a modular fashion. Ensemble and consensus analysis techniques employed within the modules are redesigned such that the compactness and interpretability of the resulting models is optimized in addition to the predictive accuracy and robustness. The framework was applied to real-word biomedical problems, with a focus on cancer biology, providing the following main results: (1) The identification of a novel tumour marker gene in collaboration with the Nottingham Queens Medical Centre, facilitating the distinction between two clinically important breast cancer subtypes (framework tool: ArrayMining) (2) The prediction of novel candidate disease genes for Alzheimer’s disease and pancreatic cancer using an integrative analysis of cellular pathway definitions and protein interaction data (framework tool: PathExpand, collaboration with the Spanish National Cancer Centre) (3) The prioritization of associations between disease-related processes and other cellular pathways using a new rule-based classification method integrating gene expression data and pathway definitions (framework tool: Top-scoring pathway pairs) (4) The discovery of topological similarities between differentially expressed genes in cancers and cellular pathway definitions mapped to a molecular interaction network (framework tool: TopoGSA, collaboration with the Spanish National Cancer Centre) In summary, the framework combines the synergies of multiple cross-domain analysis techniques within a single easy-to-use software and has provided new biological insights in a wide variety of practical settings

Application of machine learning techniques yields improvements in the predictive ability of urine biomarker panels for prostate cancer; analysis of the Movember GAP1 Urine Biomarker project.

Prostate cancer is a considerable clinical problem worldwide, with large amounts of variation seen in the clinical outcome of patients with apparently similar disease. The diagnostic and prognostic tool-sets currently available to clinicians lack both sensitivity and specificity, not taking into account the molecular variability of the disease. The successful development of non-invasive prognostic biomarker tests has the potential to impact the large numbers of patients with a clinical suspicion of prostate cancer but that ultimately do not require invasive investigation and stressful follow-up. The Movember Global Action Plan 1 (GAP1) Urine Biomarker Consortium had the aim of developing of a muti-modal urine test for the accurate discrimination of disease status. The consortium of 12 collaborating institutes collected 1,258 urine samples that were subsequently assayed by a range of biochemical techniques. The main aim of this thesis was to apply statistical learning techniques to these data in order to robustly develop prognostic models for prostate cancer. The Prostate Urine Risk (PUR) model was developed using solely NanoString data from cell-free RNA samples, and reported strong utility for predicting the outcome of an initial prostate biopsy (AUCs > 0.70 for Gleason 3+4 and 4+3). Addition-ally displaying remarkable use in an active surveillance sub-cohort, PUR identified patients at a higher apparent risk of disease progression, reporting a hazard ratio = 8.23 (95% CI: 3.26 - 20.81). The effects of altering the statistical methodology applied to the data were quantified, where ensemble algorithms presented the best solution to capturing the most amount of information. Using this information a machine learning framework was de-signed to produce multivariable risk prediction models incorporating strong internal validation compliant with the TRIPOD reporting guidelines. This framework was used to construct three risk models, each integrating information from different fractions of urine. All showed strong potential for clinical utility, reporting AUCs in excess of 0.8 for predicting Gleason 3+4, and approaching AUC = 0.9 for ruling out the presence of any cancer on biopsy. The net benefit of adopting these risk models was determined via simulation of a population-level cohort, where each model has the potential to result in large reductions to the numbers of unnecessary biopsies currently undertaken. In conclusion, the analyses presented here demonstrate the large amount of information that can be captured within urine. If these models are validated in future studies by the proposed clinical trial designs they could dramatically change the treatment pathway for prostate cancer, reducing costs to healthcare systems and ultimately unnecessary stress to patients