# Functional lipid analysis via index-based lipidomics profile: a new computational module in LipidOne

**Authors:** Husam B R Alabed, Dorotea Frongia Mancini, Martina Pergola, Luigina Romani, Sabata Martino, Albert Koulman, Roberto Maria Pellegrino

PMC · DOI: 10.1093/bioinformatics/btag090 · Bioinformatics · 2026-03-01

## TL;DR

This paper introduces a new computational tool in LipidOne that translates lipidomic data into functional insights, helping researchers understand lipid roles in health and disease.

## Contribution

The novel Functional Lipid Analysis (FLA) module computes 42 lipid function indices for systems-level interpretation.

## Key findings

- FLA computes 42 indices related to membrane structure, energy storage, and signaling from lipidomic data.
- Indices are annotated and linked to predicted protein mediators for pathway-based interpretation.
- Application to published datasets confirmed prior findings and revealed new functional insights.

## Abstract

Understanding the functional roles of lipids is essential for interpreting metabolic phenotypes in health, disease, and dietary interventions. However, lipidomic analyses typically focus on individual lipid species, making it difficult to extract mechanistic and systems-level insights. We therefore asked how quantitative lipidomic data can be translated into biologically structured and function-oriented interpretations.

Here, we present a major update to LipidOne (lipidone.eu), introducing the novel analytical module: Functional Lipid Analysis (FLA). FLA computes 42 indices describing lipid functions related to membrane structure, energy storage, and signaling. Indices are derived from lipid classes and fatty acyl-, alkyl-, and alkenyl-chain composition, statistically compared across experimental groups, and explored using multivariate and visualization tools. Each index is semantically annotated and linked to predicted protein mediators, enabling pathway- and network-based interpretation. Application to published datasets confirmed previous conclusions while uncovering additional biologically coherent functional insights.

New FLA module is freely available through LipidOne.eu web platform. The LipidOne FLA core R script (v1.0.0) is archived on Zenodo (DOI: 10.5281/zenodo.18468230). The LipidOne web platform is available at https://lipidone.eu.

## Full-text entities

- **Genes:** PDK4 (pyruvate dehydrogenase kinase 4) [NCBI Gene 5166], SCD (stearoyl-CoA desaturase) [NCBI Gene 6319] {aka FADS5, MSTP008, SCD1, SCDOS, hSCD1}, CERS1 (ceramide synthase 1) [NCBI Gene 10715] {aka EPM8, LAG1, LASS1, UOG1}, CERS2 (ceramide synthase 2) [NCBI Gene 29956] {aka L3, LASS2, SP260, TMSG1}, LOX (lysyl oxidase) [NCBI Gene 4015] {aka AAT10}, PNPLA2 (patatin like domain 2, triacylglycerol lipase) [NCBI Gene 57104] {aka 1110001C14Rik, ATGL, FP17548, PEDF-R, TTS-2.2, TTS2}, AGPAT2 (1-acylglycerol-3-phosphate O-acyltransferase 2) [NCBI Gene 10555] {aka 1-AGPAT2, BSCL, BSCL1, LPAAB, LPAAT-beta, LPLAT2}, SGMS1 (sphingomyelin synthase 1) [NCBI Gene 259230] {aka MOB, MOB1, SMS1, TMEM23, hmob33}, PDHA1 (pyruvate dehydrogenase E1 subunit alpha 1) [NCBI Gene 5160] {aka E1alpha, PDHA, PDHAD, PDHCE1A, PHE1A}, COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}, SGMS2 (sphingomyelin synthase 2) [NCBI Gene 166929] {aka CDL, SMS2}, PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], DGAT2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 84649] {aka ARAT, GS1999FULL, HMFN1045}, ACSL1 (acyl-CoA synthetase long chain family member 1) [NCBI Gene 2180] {aka ACS1, FACL1, FACL2, LACS, LACS1, LACS2}, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) [NCBI Gene 10558] {aka ALS27, HSAN1, HSN1, LBC1, LCB1, SPT1}, LCAT (lecithin-cholesterol acyltransferase) [NCBI Gene 3931], LPL (lipoprotein lipase) [NCBI Gene 4023] {aka HDLCQ11, LIPD}
- **Diseases:** HCC (MESH:D006528), chronic hepatitis C virus (MESH:D019698), cardiometabolic and neurodegenerative disorders (MESH:D019636), diseases (MESH:D004194), inflammation (MESH:D007249)
- **Chemicals:** acyl-carnitines (MESH:C116917), PC (MESH:C053518), saccharides (MESH:D002241), fatty acid (MESH:D005227), phosphatidylcholines (MESH:D010713), PUFA (MESH:D005231), lysophospholipid (MESH:D008246), glycerol (MESH:D005990), AA (-), eicosanoid (MESH:D015777), Sphingomyelin (MESH:D013109), ether (MESH:D004986), DHA (MESH:C027493), diglycerides (MESH:D004075), LIPID (MESH:D008055), PE (MESH:D010714), TG (MESH:D014280), phosphate (MESH:D010710), CE (MESH:D002563), Ceramide (MESH:D002518), phospholipids (MESH:D010743), water (MESH:D014867), cardiolipin (MESH:D002308)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

96 references — full list in the complete paper: https://tomesphere.com/paper/PMC12970596/full.md

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Source: https://tomesphere.com/paper/PMC12970596