Mehrdad Shoeibi

Mehrdad Shoeibi, Elias Hossain, Ivan Garibay et al.

Learning from weak or proxy supervision is common when ground-truth labels are unavailable, yet robustness under distribution shift remains poorly understood, especially when the supervision mechanism itself changes. We formalize this as supervision drift, defined as changes in P(y | x, c) across contexts, and study it in CRISPR-Cas13d experiments where guide efficacy is inferred indirectly from RNA-seq responses. Using data from two human cell lines and multiple time points, we build a controlled non-IID benchmark with explicit domain and temporal shifts while keeping the weak-label construction fixed. Models achieve strong in-domain performance (ridge R^2 = 0.356, Spearman rho = 0.442) and partial cross-cell-line transfer (rho ~ 0.40). However, temporal transfer fails across all models, with negative R^2 and near-zero correlation (e.g., XGBoost R^2 = -0.155, rho = 0.056). Additional analyses confirm this pattern. Feature-label relationships remain stable across cell lines but change sharply over time, indicating that failures arise from supervision drift rather than model limitations. These findings highlight feature stability as a simple diagnostic for detecting non-transferability before deployment.

Elias Hossain, Mehrdad Shoeibi, Ivan Garibay et al.

We propose CITE V.1, an agentic, evidence-grounded framework that leverages Large Language Models (LLMs) to provide transparent and reproducible interpretations of RNA-seq clusters. Unlike existing enrichment-based approaches that reduce results to broad statistical associations and LLM-only models that risk unsupported claims or fabricated citations, CITE V.1 transforms cluster interpretation by producing biologically coherent explanations explicitly anchored in the biomedical literature. The framework orchestrates three specialized agents: a Retriever that gathers domain knowledge from PubMed and UniProt, an Interpreter that formulates functional hypotheses, and Critics that evaluate claims, enforce evidence grounding, and qualify uncertainty through confidence and reliability indicators. Applied to Salmonella enterica RNA-seq data, CITE V.1 generated biologically meaningful insights supported by the literature, while an LLM-only Gemini baseline frequently produced speculative results with false citations. By moving RNA-seq analysis from surface-level enrichment to auditable, interpretable, and evidence-based hypothesis generation, CITE V.1 advances the transparency and reliability of AI in biomedicine.