bioRxiv Science⌕ Search

bioRxiv · 10.1101/719542

Variational Autoencoders for Cancer Data Integration: Design Principles and Computational Practice

Abstract

International initiatives such as the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) are collecting multiple data sets at different genome-scales with the aim to identify novel cancer bio-markers and predict patient survival. To analyse such data, several machine learning, bioinformatics and statistical methods have been applied, among them neural networks such as autoencoders. Although these models provide a good statistical learning framework to analyse multi-omic and/or clinical data, there is a distinct lack of work on how to integrate diverse patient data and identify the optimal design best suited to the available data.\n\nIn this paper, we investigate several autoencoder architectures that integrate a variety of cancer patient data types (e.g., multi-omics and clinical data). We perform extensive analyses of these approaches and provide a clear methodological and computational framework for designing systems that enable clinicians to investigate cancer traits and translate the results into clinical applications. We demonstrate how these networks can be designed, built and, in particular, applied to tasks of integrative analyses of heterogeneous breast cancer data. The results show that these approaches yield relevant data representations that, in turn, lead to accurate and stable diagnosis.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Simidjievski, N., Bodnar, C., Tariq, I., Scherer, P., Andres-Terre, H., Shams, Z., Jamnik, M., Lio', P.. 2019-07-30. Variational Autoencoders for Cancer Data Integration: Design Principles and Computational Practice. https://doi.org/10.1101/719542

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

StableProt: Structure-Aware Deep Learning for Protein Thermostability (Tm) and Environmental Adaptation (OGT) Prediction

Predicting protein melting temperature (Tm) and organismal optimal growth temperature (OGT) is essential for enzyme engineering, biocatalyst design, and metagenomic bioprospecting, yet computational prediction faces several fundamental bottlenecks: sequence-only representations miss tertiary packing; dual-task coupling induces destructive gradient conflict; natural database skew (>87% mesophiles) drives mesophilic collapse; and existing tools produce uncalibrated point predictions. To address these challenges, we present StableProt, a structure-aware framework that couples amino acid sequences with Foldseek 3Di structural tokens via a frozen SaProt backbone to capture 3D contacts. Disjoint heads condition thermodynamic stability on ecological context without gradient conflict, while targeted 14% mesophilic subsampling expands thermophile representation to eliminate mesophilic collapse. Calibrated ensemble modeling reduces calibration error to 1.92%, providing dependable 95% confidence intervals. Evaluating models across 10{degrees}C temperature intervals reveals severe baseline collapse at thermal extremes, whereas StableProt maintains robust accuracy across regimes. On ProThermDB and zero-shot FireProtDB, StableProt achieves state-of-the-art probabilistic accuracy (CRPS = 4.52{degrees}C and 8.71{degrees}C) while recovering 92.0% of hyperthermophiles ([≥]80{degrees}C), and in prospective validation, its calibrated intervals capture both enzyme stability (75.3% coverage) and host environmental growth temperatures (78.1% coverage). StableProt is freely accessible as an interactive web server at https://stableprot.dixitlab.org/.

bioinformatics↗

RoDPAA: A Robust Dissimilarity-Based Principal Angle Analysis Framework for Multi-View Microbiome Data Integration

Multiview microbiome studies profile the same participants across body sites or molecular layers, but integration is hampered by sparse, compositional data, modest sample sizes and methods that recognize only exact sharing. We present RoDPAA (Robust Dissimilarity-based Principal Angle Analysis), a framework that represents each view through any data-appropriate dissimilarity, such as Bray--Curtis, without log-ratio transformation or likelihood assumptions. RoDPAA aligns view-specific signal subspaces through principal angles, captures complete and partial sharing, and tests by permutation how many components are shared, using only eigendecomposition and little tuning. In Gaussian simulations, RoDPAA matched JIVE and MOFA given true ranks, ran faster and alone recovered the shared dimension in every replicate. In two inflammatory bowel disease (IBD) cohorts with sparse, zero-inflated data, Bray--Curtis-based RoDPAA recovered shared structure that was stable to prevalence filtering, whereas log-ratio-based alternatives were not. Its leading microbiome--metabolome factors, learned without disease labels, were the only ones associated with IBD.

bioinformatics↗

Deducing splicing events from transcript sets with splicelogic

Long-read RNA sequencing captures a greater proportion of full-length transcripts, enabling more accurate isoform identification, discovery of novel isoforms, and more precise differential transcript usage analysis. However, comparing transcripts, whether between conditions or between sets such as novel and annotated isoforms, yields complex isoform changes that are hard to manipulate, summarize, and visualize. This is compounded by vertical integration of some tools, where downstream analysis depends on the specific output of a particular upstream tool. To address this gap, we have developed splicelogic, an R/Bioconductor package that makes transcript-set comparisons biologically interpretable by turning them into discrete splicing events, such as exon skipping, alternative splice sites, intron retention, and alternative transcription start and end sites. We designed splicelogic to integrate easily with existing RNA-seq workflows and tools. The splicelogic functions are modular, readable, and extensible, making it easy for users to adapt core logic to their own custom scientific questions or novel splicing definitions. By obtaining interpretable splicing events from transcript changes, splicelogic enables downstream analyses, including annotation of RNA-binding protein recognition sites, alongside summary statistics and visualization. The splicelogic package is publicly available and distributed through Bioconductor.

bioinformatics↗