Network-Based
Analysis on Orthogonal Separation of
Human Plasma Uncovers Distinct High Density Lipoprotein Complexes
Hailong Li
Scott M. Gordon
Xiaoting Zhu
Jingyuan Deng
Debi K. Swertfeger
W. Sean Davidson
L. Jason Lu
10.1021/acs.jproteome.5b00419.s001
https://acs.figshare.com/articles/journal_contribution/Network_Based_Analysis_on_Orthogonal_Separation_of_Human_Plasma_Uncovers_Distinct_High_Density_Lipoprotein_Complexes/2143375
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.
2015-08-07 00:00:00
candidate HDL subparticles
plasma
gene knockout experiments
HDL subspecies
orthogonal chromatography techniques
graph mining algorithm
fraction
novel similarity score
CVD
complex
Human Plasma Uncovers Distinct High Density Lipoprotein ComplexesHigh density lipoprotein
function enrichment analysis