James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang and Aldons J. Lusis
Circulation Research. 2012;111:493-504, originally published August 2, 2012
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
“Good enough solutions” in the somato-gastric ganglia of lobsters. A, Schema of the somato-...
“Good enough solutions” in the somato-gastric ganglia of lobsters. A, Schema of the somato-gastric ganglion (above), whose bursting pattern controls digestive activity in the lobster (below). B, All lobsters exhibit very similar bursting activities (green and orange traces). C, However, different lobsters use different combinations of ionic conductances (left) and corresponding ion channel gene expression levels (right) to produce the nearly identical bursting patterns. Adapted from Marder,5 with permission.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
Two sets of ionic conductances [log(G/Gcontrol)] in a human ventricular action potential...
Two sets of ionic conductances [log(G/Gcontrol)] in a human ventricular action potential model that produce nearly identical action potentials and Ca transients (middle red and blue traces, respectively), for example, representing 2 “good enough solutions” for normal cardiac function. Arrows point to the conductance of IKr, an important current for repolarization, which is large in the blue action potential and small in the red action potential. If these action potentials corresponded to 2 different “good enough solutions” in real patients, the blue patient would be at greater risk for QT prolongation and torsade de pointes than the red patient if administered a drug such as erythromycin, which blocks IKr. Adapted from Sarkar and Sobie,9 with permission.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
Small-world properties in metabolic networks. A, Hypothetical arrangement of E coli's...
Small-world properties in metabolic networks. A, Hypothetical arrangement of E coli's 778 metabolites in a linear chain. If No. 525 is uridine (required for DNA synthesis and replication), its synthesis from nearby precursor metabolites such as No. 523 is highly efficient, requiring only a few steps. However, if only distant precursors such as No. 4 are available, hundreds of steps are now required, making uridine synthesis slow, inefficient, and energetically costly. B, In contrast, highly connected hub nodes (red) in a scale-free network allow efficient conversion of either No. 523 or No. 4 to uridine in only a few steps.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
A, The E coli metabolic network, displayed as a topological overlap map, in which metabolit...
A, The E coli metabolic network, displayed as a topological overlap map, in which metabolites are nodes (circles) and enzymes converting one metabolite to another are links (lines). Colors reflect the modules to which the nodes (metabolites) belong, corresponding to carbohydrate, protein, lipid, nucleic acid, aromatic, monocarbon, and coenzyme metabolism. Adapted from Ravasc et al,25 with permission. B, Log-log plot of the distribution of links per node [P(k) versus k], showing a power law distribution for both ingoing (blue) and outgoing (red) links. Adapted from Barabasi and Oltvai,50 with permission.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
A, Topological overlay map of the cardiac gene network from the HMDP. Colors indicate nodes...
A, Topological overlay map of the cardiac gene network from the HMDP. Colors indicate nodes belonging to the same gene module. B, Gene heat map of the HMDP cardiac gene network. The 8000 expressed genes are grouped on the vertical axis according to their color-coded module (on left), with the 101 HMDP strains arranged along the horizontal axis. The expression level of each gene is indicated on a red-green color scale (red indicates high; black, intermediate; green, low). C, Eigengene heat map of HMDP cardiac gene network. Expression levels of individual genes in each module have been replaced by the corresponding eigengene expression level on a red-green color scale.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
Correspondence between gene expression and “good enough solution” predictions. Left (blue)...
Correspondence between gene expression and “good enough solution” predictions. Left (blue) show histograms defining the range of conductances of 5 key EC coupling proteins (transient outward current Ito,f, the ryanodine receptor RyR, the Na-Ca exchanger NCX, the sarcoplasmic-endoplasmic reticulum Ca ATPase SERCA, and the L-type Ca current ICa,L) among 1952 computer-generated “good enough solutions” obtained using a mouse ventricular action potential model51 with a mathematical formulation of Ca cycling adapted from.52Right panels (red) show histograms of gene expression levels for the same 5 key EC coupling proteins among 100 HMDP strains. The reasonable agreement supports the hypothesis that gene expression variation in HMDP strains reflects multiplicity of functional “good enough solutions” for normal murine EC coupling.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang and Aldons J. Lusis
Circulation Research. 2012;111:493-504, originally published August 2, 2012
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
“Good enough solutions” in the somato-gastric ganglia of lobsters. A, Schema of the somato-...
“Good enough solutions” in the somato-gastric ganglia of lobsters. A, Schema of the somato-gastric ganglion (above), whose bursting pattern controls digestive activity in the lobster (below). B, All lobsters exhibit very similar bursting activities (green and orange traces). C, However, different lobsters use different combinations of ionic conductances (left) and corresponding ion channel gene expression levels (right) to produce the nearly identical bursting patterns. Adapted from Marder,5 with permission.
James N. Weiss, Alain Karma, W. Robb MacLellan, Mario Deng, Christoph D. Rau, Colin M. Rees, Jessica Wang, Nicholas Wisniewski, Eleazar Eskin, Steve Horvath, Zhilin Qu, Yibin Wang, Aldons J. Lusis
Circulation Research August 2012, 111 (4) 493-504; DOI: https://doi.org/10.1161/CIRCRESAHA.112.269084
By James N.Weiss, AlainKarma, W. RobbMacLellan, MarioDeng, Christoph D.Rau, Colin M.Rees, JessicaWang, NicholasWisniewski, EleazarEskin, SteveHorvath, ZhilinQu, YibinWang and Aldons J.Lusis
Two sets of ionic conductances [log(G/Gcontrol)] in a human ventricular action potential...
Two sets of ionic conductances [log(G/Gcontrol)] in a human ventricular action potential model that produce nearly identical action potentials and Ca transients (middle red and blue traces, respectively), for example, representing 2 “good enough solutions” for normal cardiac function. Arrows point to the conductance of IKr, an important current for repolarization, which is large in the blue action potential and small in the red action potential. If these action potentials corresponded to 2 different “good enough solutions” in real patients, the blue patient would be at greater risk for QT prolongation and torsade de pointes than the red patient if administered a drug such as erythromycin, which blocks IKr. Adapted from Sarkar and Sobie,9 with permission.
