ORIGINAL RESEARCH article

Front. Genet.

Sec. Computational Genomics

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1583756

Generalized information criteria for personalized gene network inference

Provisionally accepted
Heewon  ParkHeewon Park1*Seiya  ImotoSeiya Imoto2Sadanori  KonishiSadanori Konishi3
  • 1Sungshin Women's University, Seongbuk District, Republic of Korea
  • 2The University of Tokyo, Bunkyo, Tōkyō, Japan
  • 3Chuo University, Hachioji, Tōkyō, Japan

The final, formatted version of the article will be published soon.

Identifying individual genomic characteristics is a critical focus in personalized therapies. To reveal targets in such therapies, we considered personalized gene network analysis using kernelbased L 1 -type regularization methods. In kernel-based L 1 -type regularized modeling, selecting optimal regularization parameters is crucial because edge selection and weight estimation depend heavily on such parameters. Furthermore, selecting a kernel bandwidth that controls sample weighting is vital for personalized modeling. Although cross-validation and information criteria (i.e., AIC and BIC) are often used for parameter selection, such traditional techniques are computationally expensive or unsuitable for approaches based on estimation techniques other than maximum likelihood estimation. To overcome these issues, we introduced a novel evaluation criterion in line with the generalized information criterion (GIC), which relaxes the assumption of maximum likelihood estimation, making it suitable for personalized gene network analysis based on various estimation techniques. Monte Carlo simulations demonstrated that the proposed GIC outperforms existing evaluation criteria in terms of edge selection and weight estimation.Acute myeloid leukemia (AML) drug sensitivity-specific gene network analysis revealed critical molecular interactions to uncover ALM drugs resistant mechanism. Notably, PIK3CD activation and RARA/RELA suppression are crucial markers for improving AML chemotherapy efficacy. We also applied our strategy for gastric cancer drug sensitivity analysis and uncovered personalized therapeutic targets. We expect that the proposed sample specific GIC will be a useful tool for evaluating personalized modeling, including in sample characteristic-specific gene networks analysis.

Keywords: Model evaluation, Personalized gene network, Generalized information criteria, Acute myeloid leukemia Frontiers, Gastri cancer

Received: 27 Feb 2025; Accepted: 26 May 2025.

Copyright: © 2025 Park, Imoto and Konishi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Heewon Park, Sungshin Women's University, Seongbuk District, Republic of Korea

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