BackgroundThe optimal treatment for gender dysphoria is medical intervention, but many transgender and nonbinary people face significant treatment barriers when seeking help for gender dysphoria. When untreated, gender dysphoria is associated with depression, anxiety, suicidality, and substance misuse. Technology-delivered interventions for transgender and nonbinary people can be used discretely, safely, and flexibly, thereby reducing treatment barriers and increasing access to psychological interventions to manage distress that accompanies gender dysphoria. Technology-delivered interventions are beginning to incorporate machine learning (ML) and natural language processing (NLP) to automate intervention components and tailor intervention content. A critical step in using ML and NLP in technology-delivered interventions is demonstrating how accurately these methods model clinical constructs.ObjectiveThis study aimed to determine the preliminary effectiveness of modeling gender dysphoria with ML and NLP, using transgender and nonbinary people’s social media data.MethodsOverall, 6 ML models and 949 NLP-generated independent variables were used to model gender dysphoria from the text data of 1573 Reddit (Reddit Inc) posts created on transgender- and nonbinary-specific web-based forums. After developing a codebook grounded in clinical science, a research team of clinicians and students experienced in working with transgender and nonbinary clients used qualitative content analysis to determine whether gender dysphoria was present in each Reddit post (ie, the dependent variable). NLP (eg, n-grams, Linguistic Inquiry and Word Count, word embedding, sentiment, and transfer learning) was used to transform the linguistic content of each post into predictors for ML algorithms. A k-fold cross-validation was performed. Hyperparameters were tuned with random search. Feature selection was performed to demonstrate the relative importance of each NLP-generated independent variable in predicting gender dysphoria. Misclassified posts were analyzed to improve future modeling of gender dysphoria.ResultsResults indicated that a supervised ML algorithm (ie, optimized extreme gradient boosting [XGBoost]) modeled gender dysphoria with a high degree of accuracy (0.84), precision (0.83), and speed (1.23 seconds). Of the NLP-generated independent variables,Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5) clinical keywords (eg,dysphoriaanddisorder) were most predictive of gender dysphoria. Misclassifications of gender dysphoria were common in posts that expressed uncertainty, featured a stressful experience unrelated to gender dysphoria, were incorrectly coded, expressed insufficient linguistic markers of gender dysphoria, described past experiences of gender dysphoria, showed evidence of identity exploration, expressed aspects of human sexuality unrelated to gender dysphoria, described socially based gender dysphoria, expressed strong affective or cognitive reactions unrelated to gender dysphoria, or discussed body image.ConclusionsFindings suggest that ML- and NLP-based models of gender dysphoria have significant potential to be integrated into technology-delivered interventions. The results contribute to the growing evidence on the importance of incorporating ML and NLP designs in clinical science, especially when studying marginalized populations.