TY - JOUR
T1 - Network-Based Analysis on Orthogonal Separation of Human Plasma Uncovers Distinct High Density Lipoprotein Complexes
AU - Li, Hailong
AU - Gordon, Scott M.
AU - Zhu, Xiaoting
AU - Deng, Jingyuan
AU - Swertfeger, Debi K.
AU - Davidson, W. Sean
AU - Lu, L. Jason
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - 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 patients 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.
AB - 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 patients 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.
KW - apolipoprotein
KW - comigration pattern
KW - high-density lipoprotein
KW - human plasma
KW - maximal clique
KW - particle fractionation
KW - protein network
KW - proteomics
KW - subspecies
UR - http://www.scopus.com/inward/record.url?scp=84938816591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938816591&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.5b00419
DO - 10.1021/acs.jproteome.5b00419
M3 - Article
C2 - 26057100
AN - SCOPUS:84938816591
SN - 1535-3893
VL - 14
SP - 3082
EP - 3094
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 8
ER -