LipidSig 2.0: Integrating Lipid Characteristic Insights into Advanced Lipidomics Data Analysis

Network analysis


In the network analysis section, five distinct types of networks are provided.
Results from 'Differential Expression' are further analyzed using the 'GATOM network' , which isolates significant subnetworks within a constructed metabolite-level network. The 'Pathway activity network' computes flux changes in the lipid reaction network, facilitating the identification of active or suppressed pathways. Lastly, the 'Lipid reaction network' graphically represents significant lipid classes/species within lipid biosynthesis pathways.
In the investigated lipid classes, the 'Reactome network' aggregates reactions pertinent to these classes as documented in Reactome. The 'Lipid-related gene enrichment' analysis identifies genes associated with the lipid classes of interest, followed by an enrichment analysis to discern significant pathways.

Demo dataset source: A nutritional memory effect counteracts benefits of dietary restriction in old mice (Nat Metab. 2019)

Pathway activity network

The network provides activity pathways among lipid classes, with nodes symbolizing distinct lipid classes and lines indicating pathways, where each pathway's frequency is denoted by a pathway value, represented by the line's color (red for positive values and blue for negative values).
A table presents details about the network, including the reaction chain, pathway score, and genes involved in these pathways.
It is critical to acknowledge that lipid biochemical pathways exhibit significant variability across mammalian species, contrary to common assumptions. Thus, caution should be used when generalizing findings across species, recognizing that each may present unique lipidomic landscapes that could impact the interpretation and applicability of research outcomes.

  • Manipulate the network by clicking on the toolbar at the bottom right and left.
  • View the corresponding information of a lipid or reaction by hovering the mouse on a specific node or line.
  • For input data preparation, please refer to FAQ. You can download inputs directly from the Differential expression analysis to ensure format accuracy.





Lipid reaction network

This network illustrates the important reactions of differentially expressed lipid classes and species, where square nodes represent lipid classes and round nodes denote individual lipid species linked to those classes. The color of each node is keyed to the log2 fold change value: for round nodes, red signifies positive values, and blue indicates negative ones; for square nodes, yellow marks positive values, purple denotes negative values, and grey signifies non-significant changes or lipid classes not included in the input data.
Below the network, the two tables show the information of the network, including p-value and fold change of lipid classes and species, path, and reaction.

  • Manipulate the network by clicking on the toolbar at the bottom right and left.
  • View the corresponding information of a lipid or reaction by hovering the mouse on a specific node or line.
  • For input data preparation, please refer to FAQ. You can download inputs directly from the Differential expression analysis to ensure format accuracy.







GATOM network

The network shows the important reactions of differentially expressed lipid species. These lipids, highlighted for their distinct abundance patterns, are integrated into a comprehensive metabolic network to form an experiment-specific framework. Within this network, each node represents a differentially expressed lipid, with color variations reflecting fold change values (red indicating positive values, blue indicating negative values), and the node size corresponds to the significance level represented by the p-value.
Below the network, the two tables show the information of the network, including p-value and fold change of lipids, path, and reaction.

  • Manipulate the network by clicking on the toolbar at the bottom right and left.
  • View the corresponding information of a lipid or reaction by hovering the mouse on a specific node or line.
  • For input data preparation, please refer to FAQ. You can download inputs directly from the Differential expression analysis to ensure format accuracy.






Reactome network

The 'Reactome Network' contains the interaction of multiple lipids and genes and is summarized from the Reactome database, a curated database encompassing pathways and reactions in human biology. This function supports users to discover the metabolic networks between small molecules within Reactome Network topologies and their interactions with proteins. We integrated the reactions in these pathways and explored the inputted lipids' metabolic flow and regulatory proteins. This information will be used to build an interactive network containing different nodes, including biochemical reactions (square), small molecules (diamond), proteins (round), or complexes (triangle).
The table below the network provides the corresponding information of the network, such as path, path rank, node order, and node name.

  • Nodes representing the selected lipid classes are highlighted in larger size and red.
  • Manipulate the network by clicking on the toolbar at the bottom right and left.
  • Display or hide a specific node or line by clicking on it.



Reactome network table



Lipid-related gene enrichment

This function network of the user-defined lipid-related gene sets is presented by summarising the pathways from KEGG and Reactome databases. The mapped genes of the user-selected lipid class will be enriched and illustrated in the circular network diagram, which allows users to explore the significant functions and the relationship between lipid-related pathways and genes based on their lipid classes. The larger node size refers to more gene numbers.
The table below the network provides the corresponding information of the network, such as pathway, lipid gene number, pathway gene number, and -log10 p-value.

  • Manipulate the network by clicking on the toolbar at the bottom right and left.
  • View the corresponding information of a node or line by hovering the mouse on it.



Lipid-related gene enrichment table