{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:47:06Z","timestamp":1760233626794,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["AFR 9139104"],"award-info":[{"award-number":["AFR 9139104"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>A large percentage of the global population is currently afflicted by metabolic diseases (MD), and the incidence is likely to double in the next decades. MD associated co-morbidities such as non-alcoholic fatty liver disease (NAFLD) and cardiomyopathy contribute significantly to impaired health. MD are complex, polygenic, with many genes involved in its aetiology. A popular approach to investigate genetic contributions to disease aetiology is biological network analysis. However, data dependence introduces a bias (noise, false positives, over-publication) in the outcome. While several approaches have been proposed to overcome these biases, many of them have constraints, including data integration issues, dependence on arbitrary parameters, database dependent outcomes, and computational complexity. Network topology is also a critical factor affecting the outcomes. Here, we propose a simple, parameter-free method, that takes into account database dependence and network topology, to identify central genes in the MD network. Among them, we infer novel candidates that have not yet been annotated as MD genes and show their relevance by highlighting their differential expression in public datasets and carefully examining the literature. The method contributes to uncovering connections in the MD mechanisms and highlights several candidates for in-depth study of their contribution to MD and its co-morbidities.<\/jats:p>","DOI":"10.3390\/biology10020107","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T11:54:31Z","timestamp":1612353271000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Degree Adjusted Large-Scale Network Analysis Reveals Novel Putative Metabolic Disease Genes"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4120-1963","authenticated-orcid":false,"given":"Apurva","family":"Badkas","sequence":"first","affiliation":[{"name":"Systems Biology Group, Department of Life Sciences and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanh-Phuong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Megeno S.A., L-4362 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Caberlotto","sequence":"additional","affiliation":[{"name":"Aptuit Center for Drug Discovery and Development, 37135 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-0602","authenticated-orcid":false,"given":"Jochen G.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Saarland University Medical Center, D-66424 Homburg, Germany"},{"name":"Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-2338","authenticated-orcid":false,"given":"S\u00e9bastien","family":"De Landtsheer","sequence":"additional","affiliation":[{"name":"Systems Biology Group, Department of Life Sciences and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8225-2954","authenticated-orcid":false,"given":"Thomas","family":"Sauter","sequence":"additional","affiliation":[{"name":"Systems Biology Group, Department of Life Sciences and Medicine, University of Luxembourg, L-4365 Esch-sur-Alzette, Luxembourg"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0140-6736(05)66378-7","article-title":"The metabolic syndrome","volume":"365","author":"Eckel","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.2337\/dc08-0175","article-title":"Depression: An Important Comorbidity With Metabolic Syndrome in a General Population","volume":"31","author":"Dunbar","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S152","DOI":"10.1301\/nr.2007.dec.S152-S156","article-title":"Obesity, Metabolic Syndrome, and Type 2 Diabetes: Inflammatory Basis of Glucose Metabolic Disorders","volume":"65","author":"Pradhan","year":"2007","journal-title":"Nutr. 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