Continuous multi-omics pathway enrichment analysis resolves hidden functional heterogeneity
Sareh Amerifar1,2,3, Andreas Kopf3,4,5, Steffen Sass6,7
1MedicineII-Hematology and Oncology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Hessen, Germany.
Briefings in Bioinformatics
|June 29, 2026
Summary
JOANA, a novel Bayesian framework, enhances pathway enrichment analysis for omics data by reducing false discoveries and integrating multi-omics information. This method improves biological insight extraction from complex datasets, offering higher specificity and sensitivity.
Area of Science:
- Bioinformatics
- Computational Biology
- Genomics
Background:
- Pathway enrichment analysis is crucial for interpreting omics data.
- Existing methods face limitations like high false discovery rates and poor multi-omics integration.
Purpose of the Study:
- Introduce JOANA (Joint continuous multi-Omics enrichment ANAlysis), a Bayesian framework for robust pathway analysis.
- Address limitations of current methods for omics data interpretation.
Main Methods:
- Utilize continuous probabilistic modeling with Beta mixture distributions for significance scoring.
- Employ Bayesian networks for multi-omics data integration, handling missing values.
- Demonstrate versatility across transcriptomics, proteomics, single-cell, mutation, and epigenomics data.
Main Results:
- JOANA achieves high specificity by eliminating arbitrary thresholds.
- Integrates multi-omics data, revealing pathways missed by single-layer analyses.
- Shows up to a 20-fold reduction in reported pathways compared to existing methods while maintaining sensitivity.
Conclusions:
- JOANA offers a versatile and sensitive framework for multi-omics pathway enrichment analysis.
- The open-source Python package 'joanapy' facilitates its application.
- JOANA improves biological insight extraction from complex omics datasets.
Related Concept Videos
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:02Genomics
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:23Regulation of Expression at Multiple Steps
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...