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 gene expression data




Sparse Convex Biclustering

Jiang, Jiakun, Xiang, Dewei, Gu, Chenliang, Liu, Wei, Wang, Binhuan

arXiv.org Machine Learning

Biclustering is an essential unsupervised machine learning technique for simultaneously clustering rows and columns of a data matrix, with widespread applications in genomics, transcriptomics, and other high-dimensional omics data. Despite its importance, existing biclustering methods struggle to meet the demands of modern large-scale datasets. The challenges stem from the accumulation of noise in high-dimensional features, the limitations of non-convex optimization formulations, and the computational complexity of identifying meaningful biclusters. These issues often result in reduced accuracy and stability as the size of the dataset increases. To overcome these challenges, we propose Sparse Convex Biclustering (SpaCoBi), a novel method that penalizes noise during the biclustering process to improve both accuracy and robustness. By adopting a convex optimization framework and introducing a stability-based tuning criterion, SpaCoBi achieves an optimal balance between cluster fidelity and sparsity. Comprehensive numerical studies, including simulations and an application to mouse olfactory bulb data, demonstrate that SpaCoBi significantly outperforms state-of-the-art methods in accuracy. These results highlight SpaCoBi as a robust and efficient solution for biclustering in high-dimensional and large-scale datasets.




Scalable Single-Cell Gene Expression Generation with Latent Diffusion Models

Palla, Giovanni, Babu, Sudarshan, Dibaeinia, Payam, Pearce, James D., Li, Donghui, Khan, Aly A., Karaletsos, Theofanis, Tomczak, Jakub M.

arXiv.org Machine Learning

Computational modeling of single-cell gene expression is crucial for understanding cellular processes, but generating realistic expression profiles remains a major challenge. This difficulty arises from the count nature of gene expression data and complex latent dependencies among genes. Existing generative models often impose artificial gene orderings or rely on shallow neural network architectures. We introduce a scalable latent diffusion model for single-cell gene expression data, which we refer to as scLDM, that respects the fundamental exchangeability property of the data. Our VAE uses fixed-size latent variables leveraging a unified Multi-head Cross-Attention Block (MCAB) architecture, which serves dual roles: permutation-invariant pooling in the encoder and permutation-equivariant unpooling in the decoder. We enhance this framework by replacing the Gaussian prior with a latent diffusion model using Diffusion Transformers and linear interpolants, enabling high-quality generation with multi-conditional classifier-free guidance. We show its superior performance in a variety of experiments for both observational and perturbational single-cell data, as well as downstream tasks like cell-level classification.




Self-supervised learning on gene expression data

Dradjat, Kevin, Hamidi, Massinissa, Bartet, Pierre, Hanczar, Blaise

arXiv.org Artificial Intelligence

Predicting phenotypes from gene expression data is a crucial task in biomedical research, enabling insights into disease mechanisms, drug responses, and personalized medicine. Traditional machine learning and deep learning rely on supervised learning, which requires large quantities of labeled data that are costly and time-consuming to obtain in the case of gene expression data. Self-supervised learning has recently emerged as a promising approach to overcome these limitations by extracting information directly from the structure of unlabeled data. In this study, we investigate the application of state-of-the-art self-supervised learning methods to bulk gene expression data for phenotype prediction. We selected three self-supervised methods, based on different approaches, to assess their ability to exploit the inherent structure of the data and to generate qualitative representations which can be used for downstream predictive tasks. By using several publicly available gene expression datasets, we demonstrate how the selected methods can effectively capture complex information and improve phenotype prediction accuracy. The results obtained show that self-supervised learning methods can outperform traditional supervised models besides offering significant advantage by reducing the dependency on annotated data. We provide a comprehensive analysis of the performance of each method by highlighting their strengths and limitations. We also provide recommendations for using these methods depending on the case under study. Finally, we outline future research directions to enhance the application of self-supervised learning in the field of gene expression data analysis. This study is the first work that deals with bulk RNA-Seq data and self-supervised learning.


A Novel cVAE-Augmented Deep Learning Framework for Pan-Cancer RNA-Seq Classification

Polepalli, Vinil

arXiv.org Artificial Intelligence

Pan-cancer classification using transcriptomic (RNA-Seq) data can inform tumor subtyping and therapy selection, but is challenging due to extremely high dimensionality and limited sample sizes. In this study, we propose a novel deep learning framework that uses a class-conditional variational autoencoder (cVAE) to augment training data for pan-cancer gene expression classification. Using 801 tumor RNA-Seq samples spanning 5 cancer types from The Cancer Genome Atlas (TCGA), we first perform feature selection to reduce 20,531 gene expression features to the 500 most variably expressed genes. A cVAE is then trained on this data to learn a latent representation of gene expression conditioned on cancer type, enabling the generation of synthetic gene expression samples for each tumor class. We augment the training set with these cVAE-generated samples (doubling the dataset size) to mitigate overfitting and class imbalance. A two-layer multilayer perceptron (MLP) classifier is subsequently trained on the augmented dataset to predict tumor type. The augmented framework achieves high classification accuracy (~98%) on a held-out test set, substantially outperforming a classifier trained on the original data alone. We present detailed experimental results, including VAE training curves, classifier performance metrics (ROC curves and confusion matrix), and architecture diagrams to illustrate the approach. The results demonstrate that cVAE-based synthetic augmentation can significantly improve pan-cancer prediction performance, especially for underrepresented cancer classes.