Inside Genebench-Pro

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.

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

patient_id

analysis_set

age

sex

site

calendar_period

ecog

tumor_burden

prior_lines

prior_resistance

lineage_class

therapy_class

assessed16

benefit16

tox_stop_8wk

time_zero_day

MTB0001

1

73.8

M

S1

P2

2

0.787

3

1

A

TXR1i

0

1

0

MTB0002

1

55.2

M

S3

P1

1

2.637

0

1

A

TXR1i

1

0

0

0

MTB0003

1

68.8

F

S4

P2

0

0.891

2

1

A

TXR1i

1

1

1

0

MTB0004

1

82.8

F

S2

P2

2

4.101

0

0

B

TXR1i

1

0

0

0

MTB0005

1

65.5

F

S1

P3

1

7.0

1

1

A

TXR1i

1

0

0

0

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_id

nominal_target

chr

coord

strand

dist_lnc_tss_bp

dist_neighbor_tss_bp

guide_gc_frac

g001

LINC473

chr7

100014

14

30

0.624

g002

LINC473

chr7

100035

43

67

0.584

g003

LINC473

chr7

100051

116

56

0.622

g004

LINC473

chr7

100066

59

66

0.617

g005

LINC473

chr7

100088

74

77

0.715

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

snp

pos_bp

effect_allele

other_allele

maf

beta

se

pval

rs200000

50000000

A

C

0.42215

0.006438668310706808

0.003267330091203412

0.04876727714241972

rs200001

50010126

A

C

0.05709

0.011008993337581301

0.006955239208750407

0.11345916603941006

rs200002

50020253

G

T

0.09021

0.009922014757116319

0.005633023027015518

0.07817048492026045

rs200003

50030379

G

T

0.48399

0.010569215614164573

0.0032291419740237445

0.0010638520681901973

rs200004

50040506

A

G

0.37703

0.007036551378238654

0.0033297592321269802

0.034580976884336506

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

sample_id

collection

ancestry

family_history_tier

S_EUR_0001

screening

EUR

0

S_EUR_0002

screening

EUR

0

S_EUR_0003

screening

EUR

0

S_EUR_0004

screening

EUR

0

S_EUR_0005

screening

EUR

1

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

cell_id

donor

total_umi

HBB

IFI6

ISG15

LST1

CXCL10

D01_C001

D01

1113

7

3

4

83

5

D01_C002

D01

1103

6

3

3

112

10

D01_C003

D01

1141

9

8

12

63

9

D01_C004

D01

1250

7

60

43

2

17

D01_C005

D01

1045

9

1

2

51

15

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

sample_id

case

age

age_band

sex

pc1

pc2

pc3

ancestry_group

clinic_stratum

recruitment_stream

Q00012

1

50.45

50_64

0

-1.01514

-0.21032

-0.08849

EUR

tertiary

clinic

Q00028

0

57.39

50_64

0

-1.25987

-0.12498

0.2344

EUR

regional

registry

Q00029

1

68.4

65_plus

0

0.91598

0.62177

0.01891

AFR

tertiary

clinic

Q00030

1

74.07

65_plus

1

0.21125

-0.59634

-0.08197

EAS

community

registry

Q00032

1

82.82

65_plus

0

-1.12034

-0.24372

0.14665

EUR

community

clinic

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

bin_id

chrom

start

end

gc_content

mappability

re_sites

0

chr8

400000

420000

0.46199033821572594

0.9787574214704273

5

1

chr8

420000

440000

0.5044124208534677

0.8901084943498397

5

2

chr8

440000

460000

0.43218451584938194

0.9056879289326712

3

3

chr8

460000

480000

0.4733197282681218

0.9376529840664789

3

4

chr8

480000

500000

0.4444956062150748

0.8682565517981877

4

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_id

chr

pos_cM

m2_065

2

59.762431265596575

m2_103

2

94.52656615104739

m2_107

2

98.18761427503033

m2_079

2

72.20130244108847

m1_054

1

49.907510212292195

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

chrom

hap

start_morgan

end_morgan

anc

posterior

low_complexity_frac

chr1

h1

0.03

0.505

A

0.985

0.08

chr1

h1

0.505

0.535

B

0.62

0.92

chr1

h1

0.535

1.478849

A

0.985

0.08

chr1

h1

1.503727

1.852681

B

0.985

0.08

chr1

h1

1.852681

2.422373

A

0.985

0.08

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

generation

alt_reads

total_reads

seq_error

sample_year

6

36

40

0.16

-4500

12

34

45

0.16

-4278

18

41

55

0.16

-4056

24

38

70

0.16

-3833

30

36

90

0.16

-3611

Read-count time series for locus A.