EndoTime

EndoTime refines temporal estimates of luteal-phase endometrial biopsies using gene expression to improve timing accuracy relative to urinary ovulation tests.

Key Features:

• Gene Expression Profiling: Uses RTq-PCR measurements of six genes (IL2RB, IGFBP1, CXCL14, DPP4, GPX3, SLC15A2) across 664 endometrial biopsies collected 4–12 days after a self-reported positive home ovulation test.
• Continuous Temporal Modeling: Employs a non-categorical, continuous modeling approach to represent temporal expression profiles rather than discrete phase classification.
• Iterative Refinement: Iteratively updates sample timing estimates by modeling the temporal expression profile of each gene until convergence, preserving the overall distribution of time points.
• Validation and Accuracy: Demonstrates sharper temporal expression profiles when samples are ordered by EndoTime estimates versus patient-reported times (Wilcoxon rank-sum test) and shows congruency between RTq-PCR and RNA-sequencing (Pearson correlation: P = 8.6e-10, R² = 0.687).
• Batch Correction: Incorporates batch correction mechanisms, with larger sample batches contributing to improved timing accuracy.

Scientific Applications:

• Luteal-phase temporal profiling: Provides refined timing estimates for luteal-phase endometrial samples to enable more precise temporal characterization.
• Implantation and pregnancy loss research: Supports studies of implantation failure and recurrent pregnancy loss where accurate endometrial timing is critical.

Methodology:

Uses RTq-PCR expression of six marker genes to model continuous temporal expression profiles, iteratively refines sample timing estimates by updating gene-specific temporal models until convergence, applies batch correction, and validates ordering with the Wilcoxon rank-sum test and Pearson correlation between RTq-PCR and RNA-sequencing (P = 8.6e-10, R² = 0.687).