ArticleMolecular systems biology2010
Dissecting spatio-temporal protein networks driving human heart development and related disorders.
Article in Molecular systems biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Network physiology in space: vision and perspectives on exploring physiological networks during spaceflight for the benefit of life on earth.Frontiers in network physiology · 2026Article
- Cardiac Transcription Factors and Regulatory Networks.Advances in experimental medicine and biology · 2024Review
- Systems analysis of de novo mutations in congenital heart diseases identified a protein network in the hypoplastic left heart syndrome.Cell systems · 2022Article
- Identification of Drug-Disease Associations Using a Random Walk with Restart Method and Supervised Learning.Computational and mathematical methods in medicine · 2022Article
- Mass Spectrometry Imaging of Fibroblasts: Promise and Challenge.Expert review of proteomics · 2021Review
- The developmental origins of sex-biased expression in cardiac development.Biology of sex differences · 2019Article
- Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis.Journal of the American Heart Association · 2019Article
- In Vivo Phosphoproteome Analysis Reveals Kinome Reprogramming in Hepatocellular Carcinoma.Molecular & cellular proteomics : MCP · 2018Article
- Integrated rare variant-based risk gene prioritization in disease case-control sequencing studies.PLoS genetics · 2017Article
- Advances in MALDI imaging mass spectrometry of proteins in cardiac tissue, including the heart valve.Biochimica et biophysica acta. Proteins and proteomics · 2017Review
- Primary Cilia and Coordination of Receptor Tyrosine Kinase (RTK) and Transforming Growth Factor β (TGF-β) Signaling.Cold Spring Harbor perspectives in biology · 2017Review
- Heart Failure in Pediatric Patients With Congenital Heart Disease.Circulation research · 2017Review
- Comprehensive Analyses of Tissue-Specific Networks with Implications to Psychiatric Diseases.Methods in molecular biology (Clifton, N.J.) · 2017Article
- The extraction of drug-disease correlations based on module distance in incomplete human interactome.BMC systems biology · 2016Article
- Focus on the emerging new fields of Network Physiology and Network Medicine.New journal of physics · 2016Article
- Family Based Whole Exome Sequencing Reveals the Multifaceted Role of Notch Signaling in Congenital Heart Disease.PLoS genetics · 2016Article
- Systems biology: An emerging strategy for discovering novel pathogenetic mechanisms that promote cardiovascular disease.Global cardiology science & practice · 2016Review
- Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects.PLoS biology · 2016Article
- Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation.Human molecular genetics · 2016Article
- Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.Human genetics · 2016Article
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Authors and funding
21 authors.
Funding
Abstract
Aberrant organ development is associated with a wide spectrum of disorders, from schizophrenia to congenital heart disease, but systems-level insight into the underlying processes is very limited. Using heart morphogenesis as general model for dissecting the functional architecture of organ development, we combined detailed phenotype information from deleterious mutations in 255 genes with high-confidence experimental interactome data, and coupled the results to thorough experimental validation. Hereby, we made the first systematic analysis of spatio-temporal protein networks driving many stages of a developing organ identifying several novel signaling modules. Our results show that organ development relies on surprisingly few, extensively recycled, protein modules that integrate into complex higher-order networks. This design allows the formation of a complicated organ using simple building blocks, and suggests how mutations in the same genes can lead to diverse phenotypes. We observe a striking temporal correlation between organ complexity and the number of discrete functional modules coordinating morphogenesis. Our analysis elucidates the organization and composition of spatio-temporal protein networks that drive the formation of organs, which in the future may lay the foundation of novel approaches in treatments, diagnostics, and regenerative medicine.
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