Study

Enformer Recognizes cis-Regulated Genes by Prediction Magnitude but Fails to Predict Effect Direction: A Magnitude–Direction Dissociation in Individual-Level Expression Prediction

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We cross-reference Enformer's individual-level per-gene Pearson R (Sasse et al.

Abstract

We cross-reference Enformer's individual-level per-gene Pearson R (Sasse et al. 2023, Nature Genetics, ROSMAP cohort n=839) with GTEx v8 Brain Cortex eGenes (n=9,082) across 6,808 genes, and report a fundamental dissociation: prediction magnitude (|R|) monotonically predicts cis-eQTL gene identity (eGene rate 31.6% → 82.5%; |R| model AIC=8274 vs R+R² AIC=8378, ΔAIC=104), but prediction direction for eGenes is near-random (54.0% correct; max D10=62.5%). Direction errors are irreversible by fine-tuning on ROSMAP (Mann–Whitney p≈10⁻¹⁰⁰), yet PrediXcan recovers correct direction for R<0 eGenes (PrediXcanR=0.295), consistent with the hypothesis that Enformer's non-brain ENCODE training corpus lacks the brain-specific regulatory programs needed to correctly orient directional effects.

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Scientific commitafac6658d57b
Result tables5
CoverageComplete
LicenseMIT License

Source inventory

Deterministically extracted immutable study materials.

Repositories1
Result tables5
Charts4
Released figures0
Source datasets5
Complete tables5

Extracted study record

Authoritative metadata and released result artifacts.

The preserved source contains 5 result tables; 5 have complete deterministic representation coverage.

Gene Ids And Positions source data

58302 materialized released rows from Data/gene-ids-and-positions.tsv.

Evidence visualization

Gene Ids And Positions source data

58302 materialized released rows from Data/gene-ids-and-positions.tsv.

Browse source data · 58,302 rows

Rows 1–10 of 58302

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Gene NameGene IdChr Hg38Start Hg38End Hg38Strand Hg38Tss Hg38Chr Hg19Tss Hg19
DDX11L1ENSG0000022397211186914409+11869chr111869
WASH7PENSG0000022723211440429570-29570chr129570
MIR6859-1ENSG0000027826711736917436-17436chr117436
MIR1302-2HGENSG0000024348512955431109+29554chr129554
MIR1302-2ENSG0000028433213036630503+30366chr130366
FAM138AENSG0000023761313455436081-36081chr136081
OR4G4PENSG0000026802015247353312+52473chr152473
OR4G11PENSG0000024036115759864116+57598chr157598
OR4F5ENSG0000018609216541971585+65419chr165419
AL627309.1ENSG00000238009189295133723-133723chr1133723
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File
Data/gene-ids-and-positions.tsv
Version
afac6658
Integrity
1c1bf881…a9a24f

PrediXcanCorrelationWithExpressionENSG source data

6824 materialized released rows from Data/PrediXcanCorrelationWithExpressionENSG.tsv.

Evidence visualization

PrediXcanCorrelationWithExpressionENSG source data

6824 materialized released rows from Data/PrediXcanCorrelationWithExpressionENSG.tsv.

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ENSG00000000419NaN
ENSG000000004570.205679
ENSG00000000938NaN
ENSG00000000971NaN
ENSG00000001036NaN
ENSG000000010840.327986
ENSG00000001167NaN
ENSG000000014600.287331
ENSG00000001461NaN
ENSG000000015610.365575
ENSG00000001617NaN
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File
Data/PrediXcanCorrelationWithExpressionENSG.tsv
Version
afac6658
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8681bac2…889ad1

SupplementaryTable1 source data

6820 materialized released rows from Data/SupplementaryTable1.tsv.

Evidence visualization

SupplementaryTable1 source data

6820 materialized released rows from Data/SupplementaryTable1.tsv.

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# Gene NameGene IdChr Hg38Start Hg38End Hg38Strand Hg38Tss Hg38MeanObsStdObsPearsonRfineTunedPvalueRfineTunedMeanFineTunedStdFineTunedPearsonRCAGE,Adult,BrainPvalueRCAGE,Adult,BrainMeanCAGE,Adult,BrainStdCAGE,Adult,BrainRmeanRandomRstdrandomTstatCAGE,Adult,Brain
DPM1ENSG00000000419205093486750958555-509585553.430.250.0310.3738.490.0260.0680.0472.210.0130.0280.022131.901
SCYL3ENSG000000004571169849631169894267-1698942673.020.264-0.0280.425.730.0140.1770.00.280.0050.1320.07061.198
FGRENSG0000000093812761206427635277-276352772.480.5280.0390.265.150.0480.0910.0080.780.0120.0220.015943.864
CFHENSG000000009711196651878196747504+1966518784.180.7250.0890.014.240.0360.0370.2791.430.010.0480.03346-0.425
FUCA2ENSG000000010366143494811143511690-1435116903.050.303-0.0310.3747.020.028-0.0220.5242.570.010.0290.02018-0.348
GCLCENSG0000000108465349734153616970-536169704.690.275-0.0810.0181.960.041-0.0510.1430.10.0140.0540.03873-0.108
NFYAENSG0000000116764107294541099976+410729454.070.2180.0850.0146.530.0120.1120.0010.830.0070.0580.035962.014
STPG1ENSG0000000146012435699924416934-244169343.890.2480.0930.0074.860.042-0.2260.00.050.0020.0840.05734.195
NIPAL3ENSG0000000146112441579424472976+244157946.450.208-0.0270.4289.510.065-0.0150.6672.480.0190.020.0124-0.318
ENPP4ENSG0000000156164612999346146699+461299934.920.301-0.1910.08.950.173-0.20.04.080.0890.1060.059152.733
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File
Data/SupplementaryTable1.tsv
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afac6658
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86a0dbe9…cd4009

SupplementaryTable2 source data

1091 materialized released rows from Data/SupplementaryTable2.tsv.

Evidence visualization

SupplementaryTable2 source data

1091 materialized released rows from Data/SupplementaryTable2.tsv.

Browse source data · 1,091 rows

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# Gene NameGene IdChr Hg38Start Hg38End Hg38Strand Hg38Tss Hg38LociDriverhg38DisttoTSSISMSumISMPearsonRtoCAGE,Adult,BrainDriverPearsonRtoCAGE,Adult,BrainDecreasedFractionofSumPearsonRWithoutDrivertoCAGE,Adult,BrainIncreasedFractionofSumPearonRbyrankedDrivertoCAGE,Adult,BrainNIndividualsWithSNVFractionIndividualsWithSNVIsMainDriverISMFractionofISMmaxinSNVEQTLMaxeQTLgene
STPG1ENSG0000000146012435699924416934-24416934244173894550.012650.970.971.251.050943.8True1.0-0.1076381.05414
FARP2ENSG000000066072241356243241494841+241356243241356233-10-0.992680.920.940.831.02111496.0True-0.2020.1283770.870283
DDX11ENSG00000013573123107384531104791+310738453107390156-3.138810.960.952.00.9979968.8True-1.0-0.9238212.189899
POLA2ENSG00000014138116526176265305589+65261762652619662041.042610.980.650.130.6717214.8True1.00.1552941.319672
POLA2ENSG00000014138116526176265305589+65261762652664034641-0.554690.980.960.410.3231327.0False-0.532-0.0657851.319672
STMN4ENSG0000001559282723532327258420-2725842027245507-12913-3.741490.90.820.320.3970360.6False-0.862-0.1922871.937384
STMN4ENSG0000001559282723532327258420-2725842027258225-1952.833920.90.870.050.051149.8False0.6530.0501811.937384
STMN4ENSG0000001559282723532327258420-27258420272616763256-4.338110.90.460.010.52685.9True-1.0-0.0813751.937384
ZDHHC6ENSG0000002304110112424428112446917-112446917112430594-16323-0.113280.820.710.060.0724821.4False-0.072-0.117750.763484
ZDHHC6ENSG0000002304110112424428112446917-11244691711244699679-0.473610.820.830.140.83106491.6True-0.3-0.0262990.763484
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File
Data/SupplementaryTable2.tsv
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afac6658
Integrity
1618b841…3fa458

GTExWeights source data

5314 materialized released rows from fine_tuned_model/GTExWeights.csv.

Evidence visualization

GTExWeights source data

5314 materialized released rows from fine_tuned_model/GTExWeights.csv.

Browse source data · 5,314 rows

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Complete inspected source table. Open the source and verification details below for the exact released file.
TracksWeights
DNASE:cerebellum male adult (27 years) and male adult (35 years)0
DNASE:frontal cortex male adult (27 years) and male adult (35 years)0
DNASE:chorion0
DNASE:Ishikawa treated with 0.02% dimethyl sulfoxide for 1 hour-0.021459
DNASE:GM033480
DNASE:GM03348 genetically modified using transduction treated with 3 ug/mL doxycycline for 10 days0
DNASE:AG083950
DNASE:AG083960
DNASE:AG204430
DNASE:frontal cortex female adult (67 years) and female adult (80 years)0
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File
fine_tuned_model/GTExWeights.csv
Version
afac6658
Integrity
68e68810…ebd21c

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Pinned scientific commit: afac6658d57bfe6e2c1f17d9a96e3593843000a2

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Every accepted released table cell is represented by registered Evidence components; unstructured claims are not converted into numerical results.

Citation

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Scholarly publication

DongKoo Lee. Enformer Recognizes cis-Regulated Genes by Prediction Magnitude but Fails to Predict Effect Direction: A Magnitude–Direction Dissociation in Individual-Level Expression Prediction. 10.5281/zenodo.20754855.

Open publication

Pinned analysis source

https://github.com/mostafavilabuw/EnformerAssessment, commit afac6658d57bfe6e2c1f17d9a96e3593843000a2.

Open pinned source