Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference

Abstract Gene regulatory network (GRN) inference, a process of reconstructing gene regulatory rules from experimental data, has the potential to discover new regulatory rules. However, existing methods often struggle to generalize across diverse cell types and account for unseen regulators. Here, th...

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Main Authors: Guangzheng Weng, Patrick Martin, Hyobin Kim, Kyoung Jae Won
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202409990
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author Guangzheng Weng
Patrick Martin
Hyobin Kim
Kyoung Jae Won
author_facet Guangzheng Weng
Patrick Martin
Hyobin Kim
Kyoung Jae Won
author_sort Guangzheng Weng
collection DOAJ
description Abstract Gene regulatory network (GRN) inference, a process of reconstructing gene regulatory rules from experimental data, has the potential to discover new regulatory rules. However, existing methods often struggle to generalize across diverse cell types and account for unseen regulators. Here, this work presents GRNPT, a novel Transformer‐based framework that integrates large language model (LLM) embeddings from publicly accessible biological data and a temporal convolutional network (TCN) autoencoder to capture regulatory patterns from single‐cell RNA sequencing (scRNA‐seq) trajectories. GRNPT significantly outperforms both supervised and unsupervised methods in inferring GRNs, particularly when training data is limited. Notably, GRNPT exhibits exceptional generalizability, accurately predicting regulatory relationships in previously unseen cell types and even regulators. By combining LLMs ability to distillate biological knowledge from text and deep learning methodologies capturing complex patterns in gene expression data, GRNPT overcomes the limitations of traditional GRN inference methods and enables more accurate and comprehensive understanding of gene regulatory dynamics.
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spelling doaj-art-95cf82700a7a4ef6b80b05f52348300d2025-01-20T13:04:19ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202409990Integrating Prior Knowledge Using Transformer for Gene Regulatory Network InferenceGuangzheng Weng0Patrick Martin1Hyobin Kim2Kyoung Jae Won3Biotech Research and Innovation Centre (BRIC)University of CopenhagenOle Maaløes Vej 5Copenhagen2200DenmarkDepartment of Computational BiomedicineCedars‐Sinai Medical CenterLos Angeles CA 90069 USADepartment of Computational BiomedicineCedars‐Sinai Medical CenterLos Angeles CA 90069 USADepartment of Computational BiomedicineCedars‐Sinai Medical CenterLos Angeles CA 90069 USAAbstract Gene regulatory network (GRN) inference, a process of reconstructing gene regulatory rules from experimental data, has the potential to discover new regulatory rules. However, existing methods often struggle to generalize across diverse cell types and account for unseen regulators. Here, this work presents GRNPT, a novel Transformer‐based framework that integrates large language model (LLM) embeddings from publicly accessible biological data and a temporal convolutional network (TCN) autoencoder to capture regulatory patterns from single‐cell RNA sequencing (scRNA‐seq) trajectories. GRNPT significantly outperforms both supervised and unsupervised methods in inferring GRNs, particularly when training data is limited. Notably, GRNPT exhibits exceptional generalizability, accurately predicting regulatory relationships in previously unseen cell types and even regulators. By combining LLMs ability to distillate biological knowledge from text and deep learning methodologies capturing complex patterns in gene expression data, GRNPT overcomes the limitations of traditional GRN inference methods and enables more accurate and comprehensive understanding of gene regulatory dynamics.https://doi.org/10.1002/advs.202409990deep learninggene regulatory networksinferencelarge language modeltemporal convolutional networktransformer
spellingShingle Guangzheng Weng
Patrick Martin
Hyobin Kim
Kyoung Jae Won
Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
Advanced Science
deep learning
gene regulatory networks
inference
large language model
temporal convolutional network
transformer
title Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
title_full Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
title_fullStr Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
title_full_unstemmed Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
title_short Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference
title_sort integrating prior knowledge using transformer for gene regulatory network inference
topic deep learning
gene regulatory networks
inference
large language model
temporal convolutional network
transformer
url https://doi.org/10.1002/advs.202409990
work_keys_str_mv AT guangzhengweng integratingpriorknowledgeusingtransformerforgeneregulatorynetworkinference
AT patrickmartin integratingpriorknowledgeusingtransformerforgeneregulatorynetworkinference
AT hyobinkim integratingpriorknowledgeusingtransformerforgeneregulatorynetworkinference
AT kyoungjaewon integratingpriorknowledgeusingtransformerforgeneregulatorynetworkinference