title: Network-Based Analysis on Orthogonal Separation of Human Plasma Uncovers Distinct High Density Lipoprotein Complexes.
abstract: High density lipoprotein (HDL) particles are blood-borne complexes whose plasma levels have been associated with protection from cardiovascular disease (CVD). Recent studies have demonstrated the existence of distinct HDL subspecies; however, these have been difficult to isolate and characterize biochemically. Here, we present the first report that employs a network-based approach to systematically infer HDL subspecies. Healthy human plasma was separated into 58 fractions using our previously published three orthogonal chromatography techniques. Similar local migration patterns among HDL proteins were captured with a novel similarity score, and individual comigration networks were constructed for each fraction. By employing a graph mining algorithm, we identified 183 overlapped cliques, among which 38 were further selected as candidate HDL subparticles. Each of these 38 subparticles had at least two literature supports. In addition, GO function enrichment analysis showed that they were enriched with fundamental biological and CVD protective functions. Furthermore, gene knockout experiments in mouse model supported the validity of these subparticles related to three apolipoproteins. Finally, analysis of an apoA-I deficient human patient's plasma provided additional support for apoA-I related complexes. Further biochemical characterization of these putative subspecies may facilitate the mechanistic research of CVD and guide targeted therapeutics aimed at its mitigation.
authors.affiliation: §Institute for Systems Biology, Jianghan University, Wuhan, Hubei, 430056, P.R. China.|†Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, Ohio 45229-3039, United States.
authors.forename: Hailong
authors.initials: H
authors.lastname: Li
authors.affiliation: ‡Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, Ohio 45237-0507, United States.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Gordon
authors.affiliation: †Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, Ohio 45229-3039, United States.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhu
authors.affiliation: †Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, Ohio 45229-3039, United States.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Deng
authors.affiliation: †Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, Ohio 45229-3039, United States.
authors.forename: Debi K
authors.initials: DK
authors.lastname: Swertfeger
authors.affiliation: ‡Center for Lipid and Arteriosclerosis Science, Department of Pathology and Laboratory Medicine, University of Cincinnati, 2120 East Galbraith Road, Cincinnati, Ohio 45237-0507, United States.
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.affiliation: †Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, MLC 7024, Cincinnati, Ohio 45229-3039, United States.
authors.forename: L Jason
authors.initials: LJ
authors.lastname: Lu
mesh_terms: D000328:Adult; D000818:Animals; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008075:Lipoproteins, HDL / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D008954:Models, Biological; D010316:Particle Size; D025941:Protein Interaction Mapping / Q000379:methods; D060066:Protein Interaction Maps; D040901:Proteomics / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D008075:Lipoproteins, HDL
keywords: apolipoprotein; comigration pattern; high-density lipoprotein; human plasma; maximal clique; particle fractionation; protein network; proteomics; subspecies