Interpreting patient-Specific risk prediction using contextual decomposition of BiLSTMs: Application to children with asthma

Background: Predictive modeling with longitudinal electronic health record (EHR) data offers great promise for accelerating personalized medicine and better informs clinical decision-making. Recently, deep learning models have achieved state-of-The-Art performance for many healthcare prediction tasks. However, deep models lack interpretability, which is integral to successful decision-making and can lead to better patient care. In this paper, we build upon the contextual decomposition (CD) method, an algorithm for producing importance scores from long short-Term memory networks (LSTMs). We extend the method to bidirectional LSTMs (BiLSTMs) and use it in the context of predicting future clinical outcomes using patients' EHR historical visits. Methods: We use a real EHR dataset comprising 11071 patients, to evaluate and compare CD interpretations from LSTM and BiLSTM models. First, we train LSTM and BiLSTM models for the task of predicting which pre-school children with respiratory system-related complications will have asthma at school-Age. After that, we conduct quantitative and qualitative analysis to evaluate the CD interpretations produced by the contextual decomposition of the trained models. In addition, we develop an interactive visualization to demonstrate the utility of CD scores in explaining predicted outcomes. Results: Our experimental evaluation demonstrate that whenever a clear visit-level pattern exists, the models learn that pattern and the contextual decomposition can appropriately attribute the prediction to the correct pattern. In addition, the results confirm that the CD scores agree to a large extent with the importance scores generated using logistic regression coefficients. Our main insight was that rather than interpreting the attribution of individual visits to the predicted outcome, we could instead attribute a model's prediction to a group of visits. Conclusion: We presented a quantitative and qualitative evidence that CD interpretations can explain patient-specific predictions using CD attributions of individual visits or a group of visits. - 2019 The Author(s).This work is supported in part by Sidra Medicine under grant (SDR200043). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Scopu

Precision medicine in the era of artificial intelligence: implications in chronic disease management.

Aberrant metabolism is the root cause of several serious health issues, creating a huge burden to health and leading to diminished life expectancy. A dysregulated metabolism induces the secretion of several molecules which in turn trigger the inflammatory pathway. Inflammation is the natural reaction of the immune system to a variety of stimuli, such as pathogens, damaged cells, and harmful substances. Metabolically triggered inflammation, also called metaflammation or low-grade chronic inflammation, is the consequence of a synergic interaction between the host and the exposome-a combination of environmental drivers, including diet, lifestyle, pollutants and other factors throughout the life span of an individual. Various levels of chronic inflammation are associated with several lifestyle-related diseases such as diabetes, obesity, metabolic associated fatty liver disease (MAFLD), cancers, cardiovascular disorders (CVDs), autoimmune diseases, and chronic lung diseases. Chronic diseases are a growing concern worldwide, placing a heavy burden on individuals, families, governments, and health-care systems. New strategies are needed to empower communities worldwide to prevent and treat these diseases. Precision medicine provides a model for the next generation of lifestyle modification. This will capitalize on the dynamic interaction between an individual's biology, lifestyle, behavior, and environment. The aim of precision medicine is to design and improve diagnosis, therapeutics and prognostication through the use of large complex datasets that incorporate individual gene, function, and environmental variations. The implementation of high-performance computing (HPC) and artificial intelligence (AI) can predict risks with greater accuracy based on available multidimensional clinical and biological datasets. AI-powered precision medicine provides clinicians with an opportunity to specifically tailor early interventions to each individual. In this article, we discuss the strengths and limitations of existing and evolving recent, data-driven technologies, such as AI, in preventing, treating and reversing lifestyle-related diseases

Using Bayesian Networks and Machine Learning to Predict Computer Science Success

Bayesian Networks and Machine Learning techniques were evaluated and compared for predicting academic performance of Computer Science students at the University of Cape Town. Bayesian Networks performed similarly to other classification models. The causal links AQ1 inherent in Bayesian Networks allow for understanding of the contributing factors for academic success in this field. The most effective indicators of success in first-year ‘core’ courses in Computer Science included the student’s scores for Mathematics and Physics as well as their aptitude for learning and their work ethos. It was found that unsuccessful students could be identified with ≈91% accuracy. This could help to increase throughput as well as student wellbeing at university

Perceptron Connectives in Knowledge Representation

We discuss the role of perceptron (or threshold) connectives in the context of Description Logic, and in particular their possible use as a bridge between statistical learning of models from data and logical reasoning over knowledge bases. We prove that such connectives can be added to the language of most forms of Description Logic without increasing the complexity of the corresponding inference problem. We show, with a practical example over the Gene Ontology, how even simple instances of perceptron connectives are expressive enough to represent learned, complex concepts derived from real use cases. This opens up the possibility to import concepts learnt from data into existing ontologies

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A Deep Learning Based Automatic Severity Detector for Diabetic Retinopathy

Automated Diabetic Retinopathy (DR) screening methods with high accuracy have the strong potential to assist doctors in evaluating more patients and quickly routing those who need help to a specialist. In this work, we used Deep Convolutional Neural Network architecture to diagnosing DR from digital fundus images and accurately classifying its severity. We train this network using a graphics processor unit (GPU) on the publicly available Kaggle dataset. We used Theano, Lasagne, and cuDNN libraries on two Amazon EC2 p2.xlarge instances and demonstrated impressive results, particularly for a high-level classification task. On the dataset of 30,262 training images and 4864 testing images, our model achieves an accuracy of 72%. Our experimental results showed that increasing the batch size does not necessarily speed up the convergence of the gradient computations. Also, it demonstrated that the number and size of fully connected layers do not have a significant impact on the performance of the model.This work was supported by Sidra Medicine (authors RA and SB), as well as a grant from the Qatar National Research Fund through National Priority Research Program (NPRP) No. 6-249-1-053 (authors SA and MA).Scopu