Inside Genebench-Pro

# Inside Genebench-Pro Source: [https://openai.com/index/genebench-pro/case-studies/](https://openai.com/index/genebench-pro/case-studies/) ## Case studies These 10 case studies showcase representative questions from GeneBench\-Pro\. Each case study includes the original prompt, datasets, and supporting materials\. For an overview of the benchmark and key findings, see the[announcement blog](https://openai.com/index/introducing-genebench-pro/)\. Note: File previews show excerpts from the full datasets\. Case study 1 ### Somatic oncology: Structural variant\-guided tumor therapy benefit\-risk decision Estimate whether a synthetic TXR1\-directed inhibitor has positive clinical utility in tumors whose target activation is driven by a structural variant\. TXR1, TXR1i, DLR1, and star\-allele labels are synthetic benchmark labels\. *The target subgroup has to be recovered from long\-read, expression, tumor\-quality, and pharmacogenomic evidence before benefit and toxicity can be interpreted as a treatment decision\.* ### Files provided to the model Registry covariates, therapy, week\-16 assessment, benefit, and early toxicity\. Case study 2 ### Functional genomics: CRISPR target validation: lncRNA transcript or genomic locus? Decide whether an apparent lncRNA dependency is transcript\-specific or driven by nearby\-locus and neighbor\-gene effects\. *Transcript\-directed evidence has to survive controls for local DNA\-locus perturbation, neighbor\-gene repression, guide swaps, GC toxicity, and plate effects\.* ### Files provided to the model Guide coordinates, targets, distances, and GC features\. Case study 3 ### Statistical genetics: Prioritizing protein drug targets in a linked genetic locus Estimate direct disease effects for two nearby proteins using cis multivariable Mendelian randomization \(cis\-MVMR\) while handling assay scale, allele orientation, winner's curse, LD, and residual local pleiotropy\. *The two proteins share a correlated locus\. The analysis has to move from marginal associations to conditional, LD\-aware disease effects on a common protein scale\.* ### Files provided to the model Screening\-stage protein association summaries for PROTA\. Case study 4 ### Clinical genomics / carrier screening: DRX1 carrier\-screening residual risk under CNV and pseudogene calibration Estimate ancestry\-specific carrier frequencies, residual risk after a negative screen, partner carrier frequency, and affected\-conceptus risk from carrier\-screening assay data\. *The residual\-risk estimate depends on pseudogene\-aware carrier calls, founder\-haplotype collapse, ancestry\-specific assay calibration, and standardization from tested partners back to the full partner roster\.* ### Files provided to the model Screening\-roster adults with ancestry and screening context\. Case study 5 ### Single\-cell genomics: Activated\-monocyte eQTL after ambient RNA correction Estimate a genotype effect on activated\-monocyte expression after removing ambient RNA and technical contamination from single\-cell RNA\-seq data\. *Ambient RNA affects both target expression and the marker panel used to call activation state, so correction has to occur before the eQTL model\.* ### Files provided to the model Per\-cell UMI counts for marker genes, contamination markers, and the target gene\. Case study 6 ### Structural genetics: Nested structural variant: expression support and clinical association Estimate whether a nested structural subhaplotype inside an anonymous inversion\-like locus has a calibrated clinical association and credible expression support\. *A nested copy\-dosage signal can be confounded by the broader inversion orientation, so dosage calibration, expression support, and clinical modeling have to remain distinct\.* ### Files provided to the model Clinical and covariate data for the full cohort\. Case study 7 ### Regulatory genomics: Measuring chromatin loop strength after structural\-variant and mapping artifact masking Quantify a focal case\-control Hi\-C loop\-strength difference after removing low\-mappability and structural\-variant artifacts from the expected\-contact background\. *The target loop is defined at 20 kb resolution, but the expected\-contact model is distorted unless low\-mappability contacts and a case\-only SV stripe are masked first\.* ### Files provided to the model Target\-resolution bin annotations\. Case study 8 ### Statistical genetics: Multi\-parent QTL mapping with founder reconstruction Map a chromosome\-1 quantitative\-trait locus in an eight\-founder recombinant population by reconstructing founder ancestry before testing the phenotype association\. *The visible marker data are biallelic, but the biological signal is founder ancestry\. A defensible analysis therefore has to reconstruct founder state, check marker orientation, and separate the QTL from a batch\-aligned nuisance peak\.* ### Files provided to the model Marker identifiers, chromosomes, and genetic\-map positions\. Case study 9 ### Population genetics: Parent\-specific ancestry and recent admixture timing Infer parent\-specific ancestry proportions and recent admixture timing from phased local\-ancestry tracts after repairing reciprocal artifacts and a chromosome\-specific label inversion\. *Ancestry fractions and pulse times both change if reciprocal tract artifacts, chromosome\-local label inversion, or map denominators are handled incorrectly\.* ### Files provided to the model Phased local\-ancestry tracts with coordinates, ancestry labels, posterior values, and QC annotations\. Case study 10 ### Population genetics: Estimating selection from noisy ancient\-DNA time series Infer which of two haploid loci is under stronger positive selection from ancient allele\-frequency time series while accounting for allele orientation, directional error, drift, and changing population size\. *Noisy ancient trajectories are not directly comparable until both loci are placed on the same derived\-allele scale and the provided sample\-level sequencing\-error values are modeled directly\.* ### Files provided to the model Read\-count time series for locus A\.