XYomics: detecting sex-dependent molecular mechanisms in omics data
Sophie Le Bars1, Mohamed Soudy1, Enrico Glaab1
1Biomedical Data Science Group, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6 Avenue du Swing, Belvaux 4367, Luxembourg.
Nucleic Acids Research
|July 30, 2026
Summary
XYomics is a new R package for analyzing sex-dependent differences in omics data. It helps uncover sex-specific and sex-dimorphic changes in diseases like Alzheimer's, crucial for precision medicine.
Area of Science:
- Bioinformatics
- Genomics
- Precision Medicine
Background:
- Sex as a Biological Variable (SABV) is crucial for understanding disease, yet current bioinformatics tools lack systematic approaches for sex-related molecular mechanisms.
- Treating sex as a confounding variable can obscure important sex-specific, sex-dimorphic, and sex-modulated biological differences.
- Existing methods often aggregate data across sexes, potentially masking critical sex-dependent disease insights.
Purpose of the Study:
- To introduce XYomics, an open-source R package designed for systematic analysis of sex-dependent alterations in biomedical omics data.
- To enable the identification of sex-specific, sex-dimorphic, and sex-modulated changes at both individual feature and systems levels.
- To facilitate the discovery of sex-specific biomarkers and disease mechanisms often missed in sex-aggregated analyses.
Main Methods:
- XYomics implements dual analytical modes: sex-disease interaction term modeling and sex-stratified analysis with non-significance filtering.
- The package integrates statistical categorization with pathway enrichment and network analysis.
- Utilizes a curated hormone signaling interactome for enhanced biological interpretation.
Main Results:
- XYomics successfully identifies sex-specific, sex-dimorphic, and sex-modulated changes in omics data.
- Demonstrated utility in single-cell RNA sequencing data from Alzheimer's disease patients, revealing largely undetected sex-dimorphic genes.
- Facilitates discovery of sex-specific biomarkers and molecular mechanisms.
Conclusions:
- XYomics provides a systematic approach to analyze sex-dependent omics data, addressing limitations of current bioinformatics tools.
- The package enhances the understanding of sex-related molecular mechanisms in diseases, supporting precision medicine initiatives.
- Enables more comprehensive discovery of sex-specific biological insights previously obscured by sex-aggregated analyses.
Related Concept Videos
The Ratio of X Chromosome to Autosomes
In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Normal male Drosophila has a ratio of one X chromosome to two sets of autosomes. In contrast, normal female Drosophila...
Proteomics
A proteome is the entire set of proteins that a cell type produces. We can study proteomes using the knowledge of genomes because genes code for mRNAs, and the mRNAs encode proteins. Although mRNA analysis is a step in the right direction, not all mRNAs are translated into proteins.
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...
Proteomics is the study of proteomes' function. It involves the large-scale systematic study of the proteome to denote the protein complement expressed by a genome. Scientist Mark Wilkins coined the term proteomics...
Genomics
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...
Dosage Compensation
In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will have...
Ribosome Profiling
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique helps...

