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Peer-reviewedCC BYBioData mining

Multi-task adversarial autoencoder for functional genomic element generation with preserved biophysical properties.

7 affiliations
  1. 1Computer Information Science Department, Universiti Teknologi PETRONAS, Seri Iskandar, Malaysia. [email protected].
  2. 2IAIICT, Ahmadu Bello University, Zaria, Nigeria. [email protected].
  3. 3Computer Information Science Department, Universiti Teknologi PETRONAS, Seri Iskandar, Malaysia. [email protected].
  4. 4Computer Information Science Department, Universiti Teknologi PETRONAS, Seri Iskandar, Malaysia.
  5. 5King Khalid University, Applied College of Muhayil Asir, Abha, Saudi Arabia.
  6. 6Department of Information Systems, College of Economics, Management and Information Systems, University of Nizwa, Al Khuwair, Oman.
  7. 7IAIICT, Ahmadu Bello University, Zaria, Nigeria.

Abstract

Generative modeling of genomic sequences presents a stringent test for deep learning, requiring the capture of long-range dependencies and functional constraints beyond local nucleotide statistics. Existing architectures frequently collapse to limited modes or reproduce shallow nucleotide distributions without encoding functional semantics. We introduce the Multi-Task Adversarial Autoencoder (MT-AAE), a hybrid generative framework that integrates adversarial regularization with auxiliary functional and biophysical objectives to enforce structured latent representations. Evaluated on an empirical human gene corpus, MT-AAE achieved a Train-on-Synthetic-Test-on-Real (TRTS) accuracy of 74.7%, compared with 41.0% for a standard GAN baseline. Stratified analysis further showed that functional discriminability increased to 89.3% when sequence lengths aligned with the model’s architectural window. Importantly, the learned representations exhibited emergent biological structure: synthetic sequences spontaneously preserved cis-regulatory syntax, including canonical TATA-box motifs recovered across 100% of generated promoter sequences without explicit rule encoding, though positional placement relative to the TSS was not statistically significant (KS p=0.90), and the high occurrence rate is partly attributable to the AT-rich composition of the generated sequences. Representation-level validation using frozen DNABERT-2 and DNABERT-S embeddings confirmed that the generated sequences retained functional information beyond shallow k-mer statistics. Cross-species evaluation on Mus musculus sequences further demonstrated species-specific learning consistent with known human–mouse regulatory divergence. The framework also mitigated mode collapse, maintaining near-uniform generation across functional classes (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}Rg ≈ 1.0\end{document}), including rare categories such as tRNAs ( < 2% of the dataset). These findings position MT-AAE as an effective framework for biologically constrained genomic sequence generation.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13040-026-00591-9.

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BibTeX
@article{adamu2026multitask,
  title = {{Multi-task adversarial autoencoder for functional genomic element generation with preserved biophysical properties.}},
  author = {Shamsuddeen Adamu and Hitham Alhussian and Said Jadid Abdulkadir and Majdy Mohamed Eltayeb Eltahir and Sallam O F Khairy and Ibrahim Hayatu Hassan and Ibrahim Muhammad Kurah and Abubakar Mukhtar and Vijayakanthan Ganesalingam and Vaishali Ravi and Yahaya Saidu},
  journal = {BioData mining},
  year = {2026},
  month = aug,
  doi = {10.1186/s13040-026-00591-9},
  url = {https://europepmc.org/article/MED/42968110},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Multi-task adversarial autoencoder for functional genomic element generation with preserved biophysical properties.
AU  - Shamsuddeen Adamu
AU  - Hitham Alhussian
AU  - Said Jadid Abdulkadir
AU  - Majdy Mohamed Eltayeb Eltahir
AU  - Sallam O F Khairy
AU  - Ibrahim Hayatu Hassan
AU  - Ibrahim Muhammad Kurah
AU  - Abubakar Mukhtar
AU  - Vijayakanthan Ganesalingam
AU  - Vaishali Ravi
AU  - Yahaya Saidu
PY  - 2026
DA  - 2026/08/03
JO  - BioData mining
DO  - 10.1186/s13040-026-00591-9
UR  - https://europepmc.org/article/MED/42968110
AB  - Generative modeling of genomic sequences presents a stringent test for deep learning, requiring the capture of long-range dependencies and functional constraints beyond local nucleotide statistics. Existing architectures frequently collapse to limited modes or reproduce shallow nucleotide distributions without encoding functional semantics. We introduce the Multi-Task Adversarial Autoencoder (MT-AAE), a hybrid generative framework that integrates adversarial regularization with auxiliary functional and biophysical objectives to enforce structured latent representations. Evaluated on an empirical human gene corpus, MT-AAE achieved a Train-on-Synthetic-Test-on-Real (TRTS) accuracy of 74.7%, compared with 41.0% for a standard GAN baseline. Stratified analysis further showed that functional discriminability increased to 89.3% when sequence lengths aligned with the model’s architectural window. Importantly, the learned representations exhibited emergent biological structure: synthetic sequences spontaneously preserved cis-regulatory syntax, including canonical TATA-box motifs recovered across 100% of generated promoter sequences without explicit rule encoding, though positional placement relative to the TSS was not statistically significant (KS p=0.90), and the high occurrence rate is partly attributable to the AT-rich composition of the generated sequences. Representation-level validation using frozen DNABERT-2 and DNABERT-S embeddings confirmed that the generated sequences retained functional information beyond shallow k-mer statistics. Cross-species evaluation on Mus musculus sequences further demonstrated species-specific learning consistent with known human–mouse regulatory divergence. The framework also mitigated mode collapse, maintaining near-uniform generation across functional classes (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}R_g ≈ 1.0\end{document}), including rare categories such as tRNAs ( < 2% of the dataset). These findings position MT-AAE as an effective framework for biologically constrained genomic sequence generation.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13040-026-00591-9.
SN  - 1756-0381
ER  -