Automated QuantMap for Rapid Quantitative Molecular Network Topology Analysis.

Automated QuantMap for rapid quantitative molecular network topology analysis.

Bioinformatics. 2013 Jul 4;
Schaal W, Hammerling U, Gustafsson MG, Spjuth O

The previously disclosed QuantMap method for grouping chemicals by biological activity utilized online services for much of the data gathering and some of the numerical analysis. The present work attempts to streamline this process by using local copies of the databases and in-house analysis. Using computational methods similar or identical to those used in the previous work, a qualitatively equivalent result was found in just a few seconds on the same dataset (collection of 18 drugs). We use the user-friendly Galaxy framework to enable users to analyze their own datasets. It is hoped that this will make the QuantMap method more practical and accessible and help achieve its goals to provide substantial assistance to drug repositioning, pharmacology evaluation and toxicology risk assessment. CONTACT:; HubMed – drug


Flux balance impact degree: A new definition of impact degree to properly treat reversible reactions in metabolic networks.

Bioinformatics. 2013 Jul 4;
Zhao Y, Tamura T, Akutsu T, Vert JP

Metabolic pathways are complex systems of chemical reactions taking place in every living cell to degrade substrates and synthesize molecules needed for life. Modeling the robustness of these networks with respect to the dysfunction of one or several reactions is important to understand the basic principles of biological network organization, and to identify new drug targets. While several approaches have been proposed for that purpose, they are computationally too intensive to analyze large networks, and do not properly handle reversible reactions.We propose a new model – the flux balance impact degree (FBID) – to model the robustness of large metabolic networks with respect to gene knock-out. We formulate the computation of the impact of one or several reaction blocking as linear programs, and propose efficient strategies to solve them. We show that the proposed method better predicts the phenotypic impact of single gene deletions on Escherichia coli than existing methods. CONTACT:, HubMed – drug


Repeated administration of dimeric apoA-IMilano/POPC to cynomolgus monkeys has drastic sustained effects on lipids, lipoproteins and apoprotein levels, and on ABCA1-mediated ex-vivo cholesterol efflux capacity, and induces formation of large particles enriched in ApoE.

J Lipid Res. 2013 Jul 4;
Kempen HJ, Gomaraschi M, Bellibas SE, Plassmann S, Zerler B, Collins HL, Adelman SJ, Calabresi L, Wijngaard PL

MDCO-216, a complex of dimeric recombinant apoA-IM and POPC, was administered to cynomolgus monkeys at 30, 100 and 300 mg/kg every second day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins and ex-vivo cholesterol efflux capacity were monitored. Results: After 7 or 20 infusions FC and PL were strongly increased and HDL-C, apoA-I and apoA-II strongly decreased. We then measured short-term effects on apoA-IM, lipids and (apo)lipoproteins (by FPLC) after the first or the last infusion. After 1st infusion PL and FC went up in the HDL region but also in the LDL and VLDL regions. ApoE shifted from HDL to LDL and VLDL regions while ApoA-IM remained located in the HDL region. On day 41, ApoE levels were 8 fold higher than on Day 1 and FC, PL and apoE resided mostly in LDL and VLDL regions. Drug infusion quickly decreased endogenous cholesterol esterification rate. ABC-A1 mediated cholesterol efflux on Day 41 was markedly increased whereas SR-B1 and ABC-G1 mediated effluxes were only weakly increased. Conclusions: strong increase of FC is due to sustained stimulation of ABCA1 mediated efflux; drop in HDL and formation of large apoE-rich particles are due to lack of LCAT activation. HubMed – drug