Figure 1

Steps 1–3: discovery, prioritization and validation. (a) Cohorts used in study, depicting flow of discovery, prioritization and validation of biomarkers from each step. (b) Discovery cohort longitudinal within-participant analysis. Phchp### is study ID for each participant. V# denotes visit number (1, 2, 3, 4, 5 or 6). (c) Discovery of possible subtypes of suicidality based on high suicidal ideation (SI) visits in the discovery cohort. Participants were clustered using measures of mood and anxiety (Simplified Affective State Scale (SASS)), as well as psychosis (PANSS Positive) (d) Differential gene expression in the Discovery cohort, number of genes identified with DE and AP methods with an internal score of 1 and above. Red, increased in expression in high SI. Blue, decreased in expression in high SI. At the discovery step probesets are identified based on their score for tracking SI with a maximum of internal points of 4 (33% (1 pt), 50% (2 pt) and 80% (4 pt)). (e) Prioritization with Convergent Functional Genomics (CFG) for prior evidence of involvement in suicide. In the prioritization step probesets are converted to their associated genes using Affymetrix annotation and GeneCards. Genes are prioritized and scored using CFG for Suicide evidence with a maximum of eight external points. Genes scoring at least 4 points out of a maximum possible of 12 points total internal and external score are carried to the validation step. (f) Validation in an independent suicide completers cohort from the coroner’s office. In the validation step biomarkers are assessed for stepwise change from the discovery groups of participants with no SI, to high SI, to suicide completion, using analysis of variance. Stringent Bonferroni correction is calculated for the total number of probesets analyzed.

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