Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Adaptive imputation of missing values for incomplete pattern classification

In classification of incomplete pattern, the missing values can either play a crucial role in the class determination, or have only little influence (or eventually none) on the classification results according to the context. We propose a credal classification method for incomplete pattern with adaptive imputation of missing values based on belief function theory. At first, we try to classify the object (incomplete pattern) based only on the available attribute values. As underlying principle, we assume that the missing information is not crucial for the classification if a specific class for the object can be found using only the available information. In this case, the object is committed to this particular class. However, if the object cannot be classified without ambiguity, it means that the missing values play a main role for achieving an accurate classification. In this case, the missing values will be imputed based on the K-nearest neighbor (K-NN) and self-organizing map (SOM) techniques, and the edited pattern with the imputation is then classified. The (original or edited) pattern is respectively classified according to each training class, and the classification results represented by basic belief assignments are fused with proper combination rules for making the credal classification. The object is allowed to belong with different masses of belief to the specific classes and meta-classes (which are particular disjunctions of several single classes). The credal classification captures well the uncertainty and imprecision of classification, and reduces effectively the rate of misclassifications thanks to the introduction of meta-classes. The effectiveness of the proposed method with respect to other classical methods is demonstrated based on several experiments using artificial and real data sets

Predicting Clinical Events by Combining Static and Dynamic Information Using Recurrent Neural Networks

In clinical data sets we often find static information (e.g. patient gender, blood type, etc.) combined with sequences of data that are recorded during multiple hospital visits (e.g. medications prescribed, tests performed, etc.). Recurrent Neural Networks (RNNs) have proven to be very successful for modelling sequences of data in many areas of Machine Learning. In this work we present an approach based on RNNs, specifically designed for the clinical domain, that combines static and dynamic information in order to predict future events. We work with a database collected in the Charit\'{e} Hospital in Berlin that contains complete information concerning patients that underwent a kidney transplantation. After the transplantation three main endpoints can occur: rejection of the kidney, loss of the kidney and death of the patient. Our goal is to predict, based on information recorded in the Electronic Health Record of each patient, whether any of those endpoints will occur within the next six or twelve months after each visit to the clinic. We compared different types of RNNs that we developed for this work, with a model based on a Feedforward Neural Network and a Logistic Regression model. We found that the RNN that we developed based on Gated Recurrent Units provides the best performance for this task. We also used the same models for a second task, i.e., next event prediction, and found that here the model based on a Feedforward Neural Network outperformed the other models. Our hypothesis is that long-term dependencies are not as relevant in this task

The effect of missing values using genetic programming on evolvable diagnosis

Medical databases usually contain missing values due the policy of reducing stress and harm to the patient. In practice missing values has been a problem mainly due to the necessity to evaluate mathematical equations obtained by genetic programming. The solution to this problem is to use fill in methods to estimate the missing values. This paper analyses three fill in methods: (1) attribute means, (2) conditional means, and (3) random number generation. The methods are evaluated using sensitivity, specificity, and entropy to explain the exchange in knowledge of the results. The results are illustrated based on the breast cancer database. Conditional means produced the best fill in experimental results