A collaborative network analysis for the interpretation of transcriptomics data in Huntington’s disease

Scientific Reports, vol. 15, pp. 1412

Abstract

Rare diseases may affect the quality of life of patients and be life-threatening. Therapeutic opportunities are often limited, in part because of the lack of understanding of the molecular mechanisms underlying these diseases. This can be ascribed to the low prevalence of rare diseases and therefore the lower sample sizes available for research. A way to overcome this is to integrate experimental rare disease data with prior knowledge using network-based methods. Taking this one step further, we hypothesized that combining and analyzing the results from multiple network-based methods could provide data-driven hypotheses of pathogenic mechanisms from multiple perspectives.We analyzed a Huntington's disease transcriptomics dataset using six network-based methods in a collaborative way. These methods either inherently reported enriched annotation terms or their results were fed into enrichment analyses. The resulting significantly enriched Reactome pathways were then summarized using the ontological hierarchy which allowed the integration and interpretation of outputs from multiple methods. Among the resulting enriched pathways, there are pathways that have been shown previously to be involved in Huntington's disease and pathways whose direct contribution to disease pathogenesis remains unclear and requires further investigation.In summary, our study shows that collaborative network analysis approaches are well-suited to study rare diseases, as they provide hypotheses for pathogenic mechanisms from multiple perspectives. Applying different methods to the same case study can uncover different disease mechanisms that would not be apparent with the application of a single method.

Authors 13

1. Ozan Özışık corresponding

   Inserm · Aix-Marseille Université

   Affiliation as printed

   Aix Marseille Univ, INSERM, MMG, Marseille, France. ozan.ozisik@inserm.fr

   Aix Marseille Univ, INSERM, MMG, Marseille, France

2. Nazli Sila Kara

   Charles University · Acıbadem University

   Affiliation as printed

   Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey

   Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic

3. Tooba Abbassi‐Daloii Aachen Department of Human Genetics

   Leiden University Medical Center · Maastricht University

   Affiliation as printed

   Department of Bioinformatics-BiGCaT, NUTRIM/MHeNs, Maastricht University, Maastricht, The Netherlands

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

4. Morgane Térézol

   Inserm · Aix-Marseille Université

   Affiliation as printed

   Aix Marseille Univ, INSERM, MMG, Marseille, France

5. Elsa C. Kuijper Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

6. Núria Queralt-Rosiñach Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

7. Annika Jacobsen Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

8. Osman Uğur Sezerman

   Acıbadem University

   Affiliation as printed

   Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey

9. Marco Roos Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

10. Chris T. Evelo

    Maastricht University

    Affiliation as printed

    Department of Bioinformatics-BiGCaT, NUTRIM/MHeNs, Maastricht University, Maastricht, The Netherlands

    Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, The Netherlands

11. Anaı̈s Baudot

    Centre National de la Recherche Scientifique · Inserm · Aix-Marseille Université · Barcelona Supercomputing Center

    Affiliation as printed

    Aix Marseille Univ, INSERM, MMG, Marseille, France

    Barcelona Supercomputing Center (BSC), Barcelona, Spain

    CNRS, Marseille, France

12. Friederike Ehrhart

    Maastricht University

    Affiliation as printed

    Department of Bioinformatics-BiGCaT, NUTRIM/MHeNs, Maastricht University, Maastricht, The Netherlands

13. Eleni Mina Aachen Department of Human Genetics

    Leiden University Medical Center

    Affiliation as printed

    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands