Dataset Information

Depression and suicide risk prediction models using blood-derived multi-omics data.

ABSTRACT: More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 92.6% in distinguishing SAs from MDD patients, 87.3% in distinguishing MDD patients from controls, and 86.7% in distinguishing SAs from controls. We also developed regression models for predicting psychiatric scales with R2 values of 0.961 and 0.943 for Hamilton Rating Scale for Depression-17 and Scale for Suicide Ideation, respectively. Multi-omics data were used to construct psychiatric status prediction models for improved mental health treatment.

SUBMITTER: Bhak Y

PROVIDER: S-EPMC6797735 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Depression and suicide risk prediction models using blood-derived multi-omics data.

Bhak Youngjune Y Jeong Hyoung-Oh HO Cho Yun Sung YS Jeon Sungwon S Cho Juok J Gim Jeong-An JA Jeon Yeonsu Y Blazyte Asta A Park Seung Gu SG Kim Hak-Min HM Shin Eun-Seok ES Paik Jong-Woo JW Lee Hae-Woo HW Kang Wooyoung W Kim Aram A Kim Yumi Y Kim Byung Chul BC Ham Byung-Joo BJ Bhak Jong J Lee Semin S

Translational psychiatry 20191017 1

More than 300 million people worldwide experience depression; annually, ~800,000 people die by suicide. Unfortunately, conventional interview-based diagnosis is insufficient to accurately predict a psychiatric status. We developed machine learning models to predict depression and suicide risk using blood methylome and transcriptome data from 56 suicide attempters (SAs), 39 patients with major depressive disorder (MDD), and 87 healthy controls. Our random forest classifiers showed accuracies of 9 ...[more]

PMID: 31624227

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Project description:BackgroundSuicide risk prediction models have been developed by using information from patients' electronic health records (EHR), but the time elapsed between model development and health system implementation is often substantial. Temporal changes in health systems and EHR coding practices necessitate the evaluation of such models in more contemporary data.ObjectivesA set of published suicide risk prediction models developed by using EHR data from 2009 to 2015 across seven health systems reported c-statistics of 0.85 for suicide attempt and 0.83 to 0.86 for suicide death. Our objective was to evaluate these models' performance with contemporary data (2014-2017) from these systems.MethodsWe evaluated performance using mental health visits (6,832,439 to mental health specialty providers and 3,987,078 to general medical providers) from 2014 to 2017 made by 1,799,765 patients aged 13+ across the health systems. No visits in our evaluation were used in the previous model development. Outcomes were suicide attempt (health system records) and suicide death (state death certificates) within 90 days following a visit. We assessed calibration and computed c-statistics with 95% confidence intervals (CI) and cut-point specific estimates of sensitivity, specificity, and positive/negative predictive value.ResultsModels were well calibrated; 46% of suicide attempts and 35% of suicide deaths in the mental health specialty sample were preceded by a visit (within 90 days) with a risk score in the top 5%. In the general medical sample, 53% of attempts and 35% of deaths were preceded by such a visit. Among these two samples, respectively, c-statistics were 0.862 (95% CI: 0.860-0.864) and 0.864 (95% CI: 0.860-0.869) for suicide attempt, and 0.806 (95% CI: 0.790-0.822) and 0.804 (95% CI: 0.782-0.829) for suicide death.ConclusionPerformance of the risk prediction models in this contemporary sample was similar to historical estimates for suicide attempt but modestly lower for suicide death. These published models can inform clinical practice and patient care today.

Project description:Multi-omics data, that is, datasets containing different types of high-dimensional molecular variables, are increasingly often generated for the investigation of various diseases. Nevertheless, questions remain regarding the usefulness of multi-omics data for the prediction of disease outcomes such as survival time. It is also unclear which methods are most appropriate to derive such prediction models. We aim to give some answers to these questions through a large-scale benchmark study using real data. Different prediction methods from machine learning and statistics were applied on 18 multi-omics cancer datasets (35 to 1000 observations, up to 100 000 variables) from the database 'The Cancer Genome Atlas' (TCGA). The considered outcome was the (censored) survival time. Eleven methods based on boosting, penalized regression and random forest were compared, comprising both methods that do and that do not take the group structure of the omics variables into account. The Kaplan-Meier estimate and a Cox model using only clinical variables were used as reference methods. The methods were compared using several repetitions of 5-fold cross-validation. Uno's C-index and the integrated Brier score served as performance metrics. The results indicate that methods taking into account the multi-omics structure have a slightly better prediction performance. Taking this structure into account can protect the predictive information in low-dimensional groups-especially clinical variables-from not being exploited during prediction. Moreover, only the block forest method outperformed the Cox model on average, and only slightly. This indicates, as a by-product of our study, that in the considered TCGA studies the utility of multi-omics data for prediction purposes was limited. Contact:moritz.herrmann@stat.uni-muenchen.de, +49 89 2180 3198 Supplementary information: Supplementary data are available at Briefings in Bioinformatics online. All analyses are reproducible using R code freely available on Github.

Project description:BackgroundSuicide risk prediction models derived from electronic health records (EHR) are a novel innovation in suicide prevention but there is little evidence to guide their implementation.MethodsIn this qualitative study, 30 clinicians and 10 health care administrators were interviewed from one health system anticipating implementation of an automated EHR-derived suicide risk prediction model and two health systems piloting different implementation approaches. Site-tailored interview guides focused on respondents' expectations for and experiences with suicide risk prediction models in clinical practice, and suggestions for improving implementation. Interview prompts and content analysis were guided by Consolidated Framework for Implementation Research (CFIR) constructs.ResultsAdministrators and clinicians found use of the suicide risk prediction model and the two implementation approaches acceptable. Clinicians desired opportunities for early buy-in, implementation decision-making, and feedback. They wanted to better understand how this manner of risk identification enhanced existing suicide prevention efforts. They also wanted additional training to understand how the model determined risk, particularly after patients they expected to see identified by the model were not flagged at-risk and patients they did not expect to see identified were. Clinicians were concerned about having enough suicide prevention resources for potentially increased demand and about their personal liability; they wanted clear procedures for situations when they could not reach patients or when patients remained at-risk over a sustained period. Suggestions for making risk model workflows more efficient and less burdensome included consolidating suicide risk information in a dedicated module in the EHR and populating risk assessment scores and text in clinical notes.ConclusionHealth systems considering suicide risk model implementation should engage clinicians early in the process to ensure they understand how risk models estimate risk and add value to existing workflows, clarify clinician role expectations, and summarize risk information in a convenient place in the EHR to support high-quality patient care.

Project description:Logical models of cancer pathways are typically built by mining the literature for relevant experimental observations. They are usually generic as they apply for large cohorts of individuals. As a consequence, they generally do not capture the heterogeneity of patient tumors and their therapeutic responses. We present here a novel framework, referred to as PROFILE, to tailor logical models to a particular biological sample such as a patient tumor. This methodology permits to compare the model simulations to individual clinical data, i.e., survival time. Our approach focuses on integrating mutation data, copy number alterations (CNA), and expression data (transcriptomics or proteomics) to logical models. These data need first to be either binarized or set between 0 and 1, and can then be incorporated in the logical model by modifying the activity of the node, the initial conditions or the state transition rates. The use of MaBoSS, a tool based on Monte-Carlo kinetic algorithm to perform stochastic simulations on logical models results in model state probabilities, and allows for a semi-quantitative study of the model phenotypes and perturbations. As a proof of concept, we use a published generic model of cancer signaling pathways and molecular data from METABRIC breast cancer patients. For this example, we test several combinations of data incorporation and discuss that, with these data, the most comprehensive patient-specific cancer models are obtained by modifying the nodes' activity of the model with mutations, in combination or not with CNA data, and altering the transition rates with RNA expression. We conclude that these model simulations show good correlation with clinical data such as patients' Nottingham prognostic index (NPI) subgrouping and survival time. We observe that two highly relevant cancer phenotypes derived from personalized models, Proliferation and Apoptosis, are biologically consistent prognostic factors: patients with both high proliferation and low apoptosis have the worst survival rate, and conversely. Our approach aims to combine the mechanistic insights of logical modeling with multi-omics data integration to provide patient-relevant models. This work leads to the use of logical modeling for precision medicine and will eventually facilitate the choice of patient-specific drug treatments by physicians.

Dataset Information

Depression and suicide risk prediction models using blood-derived multi-omics data.

Publications

Depression and suicide risk prediction models using blood-derived multi-omics data.

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