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Interpretable and accurate prediction models for metagenomics data.

ABSTRACT: BACKGROUND:Microbiome biomarker discovery for patient diagnosis, prognosis, and risk evaluation is attracting broad interest. Selected groups of microbial features provide signatures that characterize host disease states such as cancer or cardio-metabolic diseases. Yet, the current predictive models stemming from machine learning still behave as black boxes and seldom generalize well. Their interpretation is challenging for physicians and biologists, which makes them difficult to trust and use routinely in the physician-patient decision-making process. Novel methods that provide interpretability and biological insight are needed. Here, we introduce "predomics", an original machine learning approach inspired by microbial ecosystem interactions that is tailored for metagenomics data. It discovers accurate predictive signatures and provides unprecedented interpretability. The decision provided by the predictive model is based on a simple, yet powerful score computed by adding, subtracting, or dividing cumulative abundance of microbiome measurements. RESULTS:Tested on >100 datasets, we demonstrate that predomics models are simple and highly interpretable. Even with such simplicity, they are at least as accurate as state-of-the-art methods. The family of best models, discovered during the learning process, offers the ability to distil biological information and to decipher the predictability signatures of the studied condition. In a proof-of-concept experiment, we successfully predicted body corpulence and metabolic improvement after bariatric surgery using pre-surgery microbiome data. CONCLUSIONS:Predomics is a new algorithm that helps in providing reliable and trustworthy diagnostic decisions in the microbiome field. Predomics is in accord with societal and legal requirements that plead for an explainable artificial intelligence approach in the medical field.

SUBMITTER: Prifti E

PROVIDER: S-EPMC7062144 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Interpretable and accurate prediction models for metagenomics data.

Prifti Edi E Chevaleyre Yann Y Hanczar Blaise B Belda Eugeni E Danchin Antoine A Clément Karine K Zucker Jean-Daniel JD

GigaScience 20200301 3

<h4>Background</h4>Microbiome biomarker discovery for patient diagnosis, prognosis, and risk evaluation is attracting broad interest. Selected groups of microbial features provide signatures that characterize host disease states such as cancer or cardio-metabolic diseases. Yet, the current predictive models stemming from machine learning still behave as black boxes and seldom generalize well. Their interpretation is challenging for physicians and biologists, which makes them difficult to trust a ...[more]

PMID: 32150601

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Project description:BackgroundHistone Mark Modifications (HMs) are crucial actors in gene regulation, as they actively remodel chromatin to modulate transcriptional activity: aberrant combinatorial patterns of HMs have been connected with several diseases, including cancer. HMs are, however, reversible modifications: understanding their role in disease would allow the design of 'epigenetic drugs' for specific, non-invasive treatments. Standard statistical techniques were not entirely successful in extracting representative features from raw HM signals over gene locations. On the other hand, deep learning approaches allow for effective automatic feature extraction, but at the expense of model interpretation.ResultsHere, we propose ShallowChrome, a novel computational pipeline to model transcriptional regulation via HMs in both an accurate and interpretable way. We attain state-of-the-art results on the binary classification of gene transcriptional states over 56 cell-types from the REMC database, largely outperforming recent deep learning approaches. We interpret our models by extracting insightful gene-specific regulative patterns, and we analyse them for the specific case of the PAX5 gene over three differentiated blood cell lines. Finally, we compare the patterns we obtained with the characteristic emission patterns of ChromHMM, and show that ShallowChrome is able to coherently rank groups of chromatin states w.r.t. their transcriptional activity.ConclusionsIn this work we demonstrate that it is possible to model HM-modulated gene expression regulation in a highly accurate, yet interpretable way. Our feature extraction algorithm leverages on data downstream the identification of enriched regions to retrieve gene-wise, statistically significant and dynamically located features for each HM. These features are highly predictive of gene transcriptional state, and allow for accurate modeling by computationally efficient logistic regression models. These models allow a direct inspection and a rigorous interpretation, helping to formulate quantifiable hypotheses.

Project description:OBJECTIVES:Sepsis is among the leading causes of morbidity, mortality, and cost overruns in critically ill patients. Early intervention with antibiotics improves survival in septic patients. However, no clinically validated system exists for real-time prediction of sepsis onset. We aimed to develop and validate an Artificial Intelligence Sepsis Expert algorithm for early prediction of sepsis. DESIGN:Observational cohort study. SETTING:Academic medical center from January 2013 to December 2015. PATIENTS:Over 31,000 admissions to the ICUs at two Emory University hospitals (development cohort), in addition to over 52,000 ICU patients from the publicly available Medical Information Mart for Intensive Care-III ICU database (validation cohort). Patients who met the Third International Consensus Definitions for Sepsis (Sepsis-3) prior to or within 4 hours of their ICU admission were excluded, resulting in roughly 27,000 and 42,000 patients within our development and validation cohorts, respectively. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:High-resolution vital signs time series and electronic medical record data were extracted. A set of 65 features (variables) were calculated on hourly basis and passed to the Artificial Intelligence Sepsis Expert algorithm to predict onset of sepsis in the proceeding T hours (where T = 12, 8, 6, or 4). Artificial Intelligence Sepsis Expert was used to predict onset of sepsis in the proceeding T hours and to produce a list of the most significant contributing factors. For the 12-, 8-, 6-, and 4-hour ahead prediction of sepsis, Artificial Intelligence Sepsis Expert achieved area under the receiver operating characteristic in the range of 0.83-0.85. Performance of the Artificial Intelligence Sepsis Expert on the development and validation cohorts was indistinguishable. CONCLUSIONS:Using data available in the ICU in real-time, Artificial Intelligence Sepsis Expert can accurately predict the onset of sepsis in an ICU patient 4-12 hours prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed sepsis prediction model.

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Interpretable and accurate prediction models for metagenomics data.

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Interpretable and accurate prediction models for metagenomics data.

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