KEGG Spider: Interpretation of Genomics Data in the Context of the Global Gene

Scientists from Helmholtz Zentrum München have developed a breakthrough methodology for understanding metabolism related variations from experimental genomics data. Using proposed bioinformatics strategy they were able to demonstrate that in most cases identified disease-specific metabolism variations are not independent, e.g. deregulated genes from different pathways are linked to each other via one or two step of consecutive metabolic reactions. The methodology may prompt new drug development strategies to affect/change metabolism of the disease cells.

The results of the German research team, which consists of scientists from Helmholtz Zentrum München (National German Research Center for Environmental Health) have been published on 18 December 2008, in the open access journal "Genome Biology".

In the post-genomic era the targets of many clinical experimental studies are complex cell disorders. A standard experimental strategy is to compare the genetic/proteomics signature of cells in normal and anomalous states. As a result, a set of genes with differential activity is delivered. In the next step, the interpretation of identified genes in a model context is required. A widely accepted strategy is to infer biological processes that are most relevant to the analyzed gene list. The inference is based on prior knowledge of individual gene properties, such as gene biological functions or interactions. This common approach is usually referred as enrichment analysis. The major limitation of such type of analyses is an ability to understand the connections between genes from different and seems to be unrelated pathways.

In comparison to previously developed methods, KEGG spider provides a robust analytical framework for interpretation of gene lists in the context of a global gene metabolic network. The information of gene pair wise relations is widely exploited (gene A is related to gene B via metabolite C) and the inferred network model is not limited to the size of one metabolic pathway.

Examples of analysis of disease-specific genes by KEGG spider suggest that the split of metabolic reactions to canonical pathways is to some degree artificial. In most cases, metabolism-related genes were from several KEGG canonical pathways. However, the analysis with KEGG spider reveals that, if to consider the topology of the global gene metabolic network, these genes form a non-interrupted (maximum one or two gene is missing) disease-specific pathway, which run through several canonical pathways. These results also support a hypothesis that disease-specific metabolism variations in most cases are not independent, e.g. deregulated genes from different pathways are linked to each other via one or two step consecutive metabolic reactions. Of about twenty examples of analysis of disease-specific genes presented in the paper may serve as support for this hypothesis.

Reference
Antonov A.V., Dietmann S., Mewes G.W. KEGG spider: interpretation of genomics data in the context of the global gene metabolic network. Genome Biology 2008, 9:R179 doi:10.1186/gb-2008-9-12-r179.

About the Institute of Bioinformatics and Systems Biology (Munich Information Center for Protein Sequences)
The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) provides genome-related information and analyses in a systematic way. Institute supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis experimental data. For further information, please visit http://mips.gsf.de/.

Most Popular Now

Pfizer's elranatamab granted FDA Breakthrough Ther…

Pfizer Inc. (NYSE:PFE) announced its investigational cancer immunotherapy, elranatamab, received Breakthrough Therapy Designation from the U.S. Food and Drug Administrati...

Salvat Laboratories announces submission of New Dr…

Salvat Laboratories announced that it has submitted a New Drug Application (NDA) to the FDA for the approval of the first ocular corticosteroid formulated in a nanoemulsi...

Bayer with continued strong performance

The Bayer Group maintained its strong business performance across all three divisions in the third quarter. "Despite rising inflation and global supply chain problems, we...

Vividion Therapeutics names Jenna Goldberg as Chie…

Vividion Therapeutics, Inc., a biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision the...

New insights on antibody responses to Omicron vari…

Knowing how well vaccination against one SARS-CoV-2 strain (with or without previous infection) counteracts infection with a different strain is a critical research quest...

Pfizer and BioNTech receive positive CHMP opinion …

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced a booster dose of their Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine (COMIRNATY® Original/Omicron ...

Sugar molecules as a target in cancer therapy

Cancer cells use sugar molecules on their surface to disable attacks by the body's immune system. Researchers at the University of Basel now report on how this mechanism ...

COVID vaccination improves effectiveness of cancer…

Patients with nasopharyngeal cancer are often treated with drugs that activate their immune system against the tumor. Until now, it was feared that vaccination against Co...

Making melanoma immortal: Pitt scientists discover…

Scientists at the University of Pittsburgh School of Medicine have discovered the missing puzzle piece in the mystery of how melanoma tumors control their mortality. I...

New drug shows promise for fighting both COVID-19 …

While vaccination can provide life-saving protection against COVID-19, scientists are still searching for ways to treat severe infections, including in people who cannot ...

Study reveals vaccine confidence declined consider…

A new study suggests that, despite the success of the COVID-19 vaccination campaigns, vaccine confidence has declined significantly since the start of the pandemic. Re...

Sanofi and GSK's next-generation COVID-19 booster …

After the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for VidPrevtyn® Beta, the vaccine was approved by t...