title: FocusHeuristics - expression-data-driven network optimization and disease gene prediction.
abstract: To identify genes contributing to disease phenotypes remains a challenge for bioinformatics. Static knowledge on biological networks is often combined with the dynamics observed in gene expression levels over disease development, to find markers for diagnostics and therapy, and also putative disease-modulatory drug targets and drugs. The basis of current methods ranges from a focus on expression-levels (Limma) to concentrating on network characteristics (PageRank, HITS/Authority Score), and both (DeMAND, Local Radiality). We present an integrative approach (the FocusHeuristics) that is thoroughly evaluated based on public expression data and molecular disease characteristics provided by DisGeNet. The FocusHeuristics combines three scores, i.e. the log fold change and another two, based on the sum and difference of log fold changes of genes/proteins linked in a network. A gene is kept when one of the scores to which it contributes is above a threshold. Our FocusHeuristics is both, a predictor for gene-disease-association and a bioinformatics method to reduce biological networks to their disease-relevant parts, by highlighting the dynamics observed in expression data. The FocusHeuristics is slightly, but significantly better than other methods by its more successful identification of disease-associated genes measured by AUC, and it delivers mechanistic explanations for its choice of genes.
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ernst
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.|Annoroad Gene Technology, No. 88 Kechuang 6th Street, Beijing, 100176, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Du
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Warsow
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamed
authors.affiliation: Institute of Anatomy and Cell Biology, University of Greifswald, Friedrich-Loeffler-Straße 23c, Greifswald 17487, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Endlich
authors.affiliation: Institute of Anatomy and Cell Biology, University of Greifswald, Friedrich-Loeffler-Straße 23c, Greifswald 17487, Germany.
authors.forename: Karlhans
authors.initials: K
authors.lastname: Endlich
authors.affiliation: Clinic for Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Hugo
authors.initials: H
authors.lastname: Murua Escobar
authors.affiliation: Clinic for Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Lisa-Madeleine
authors.initials: LM
authors.lastname: Sklarz
authors.affiliation: Clinic for Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Sina
authors.initials: S
authors.lastname: Sender
authors.affiliation: Clinic for Hematology, Oncology and Palliative Medicine, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanß
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Möller
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fuellen
authors.affiliation: Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Struckmann
mesh_terms: D000465:Algorithms; D015415:Biomarkers; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D012372:ROC Curve
chemical_list: D015415:Biomarkers