# Linear Causal Discovery with Interventional Constraints

**Authors:** Zhigao Guo, Feng Dong

PMC · DOI: 10.1007/s10994-026-06998-z · Machine Learning · 2026-02-17

## TL;DR

This paper introduces interventional constraints to improve causal discovery by encoding known causal relationships as inequality constraints, leading to more accurate and explainable models.

## Contribution

The novel concept of interventional constraints allows encoding high-level causal knowledge as inequality constraints on causal effects.

## Key findings

- Integrating interventional constraints improves model accuracy and consistency with established findings.
- The method facilitates the discovery of new causal relationships at lower cost.
- The approach is evaluated on real-world datasets and shows promising results.

## Abstract

Incorporating causal knowledge and mechanisms is essential for refining causal models and improving downstream tasks, such as designing new treatments. In this paper, we introduce a novel concept in causal discovery, termed interventional constraints, which differs fundamentally from interventional data. While interventional data require direct perturbations of variables, interventional constraints encode high-level causal knowledge in the form of inequality constraints on causal effects. For instance, in the Sachs dataset, Akt has been shown to be activated by PIP3, meaning PIP3 exerts a positive causal effect on Akt. Existing causal discovery methods allow enforcing structural constraints (e.g., requiring a causal path from PIP3 to Akt), but they may still produce incorrect causal conclusions, such as learning that “PIP3 inhibits Akt.” Interventional constraints bridge this gap by explicitly constraining the total causal effect between variable pairs, ensuring learned models respect known causal influences. To formalize interventional constraints, we adopt a metric to quantify total causal effects for linear causal models and formulate the problem as a constrained optimization task, solved using a two-stage constrained optimization method. We evaluate our approach on real-world datasets and demonstrate that integrating interventional constraints not only improves model accuracy and ensures consistency with established findings, making models more explainable, but also facilitates the discovery of new causal relationships that would otherwise be costly to identify.

## Linked entities

- **Proteins:** AKT1 (AKT serine/threonine kinase 1), PIP3 (plasma membrane intrinsic protein 3)

## Full-text entities

- **Genes:** PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MAP2K1 (mitogen-activated protein kinase kinase 1) [NCBI Gene 5604] {aka CFC3, MAPKK1, MEK1, MEL, MKK1, PRKMK1}, HSPG2 (heparan sulfate proteoglycan 2) [NCBI Gene 3339] {aka HSPG, PLC, PRCAN, SJA, SJS, SJS1}, PIP (prolactin induced protein) [NCBI Gene 5304] {aka BRST-2, GCDFP-15, GCDFP15, GPIP4}, MAP2K4 (mitogen-activated protein kinase kinase 4) [NCBI Gene 6416] {aka JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, ZHX2 (zinc fingers and homeoboxes 2) [NCBI Gene 22882] {aka AFR1, RAF}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, MAP2K2 (mitogen-activated protein kinase kinase 2) [NCBI Gene 5605] {aka CFC4, MAPKK2, MEK2, MKK2, PRKMK2}, PDE4A (phosphodiesterase 4A) [NCBI Gene 5141] {aka DPDE2, PDE4, PDE46}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, CALM3 (calmodulin 3) [NCBI Gene 808] {aka CALM, CAM1, CAM2, CAMB, CPVT6, CaM}, YWHAQ (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta) [NCBI Gene 10971] {aka 14-3-3, 1C5, HS1}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, MAPK3 (mitogen-activated protein kinase 3) [NCBI Gene 5595] {aka ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1}
- **Diseases:** cancer (MESH:D009369), lung cancer (MESH:D008175), SID (MESH:D020914), T (MESH:D001260), CD (MESH:D003424)
- **Chemicals:** PIP2 (MESH:D019269), GraN (MESH:D017829), H89 (MESH:C063509), phospholipids (MESH:D010743), GraN-DAG (-), propranolol (MESH:D011433), phosphatidylinositol-3,4,5-trisphosphate (MESH:C060974), IBMX (MESH:D015056), forskolin (MESH:D005576), W (MESH:D014414), LPS (MESH:D008070)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913306/full.md

## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913306/full.md

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Source: https://tomesphere.com/paper/PMC12913306