Limits...
Inferring physical protein contacts from large-scale purification data of protein complexes.

Schelhorn SE, Mestre J, Albrecht M, Zotenko E - Mol. Cell Proteomics (2011)

Bottom Line: Our results show that raw purification data can indeed be exploited to determine high-confidence physical protein contacts within protein complexes.In contrast to previous findings, we observe that physical contacts inferred from purification experiments of protein complexes can be qualitatively comparable to binary protein interactions measured by experimental high-throughput assays such as yeast two-hybrid.This suggests that computationally derived physical contacts might complement binary protein interaction assays and guide large-scale interactome mapping projects by prioritizing putative physical contacts for further experimental screens.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Informatics, Saarbr├╝cken, Germany. sven@mpi-inf.mpg.de

ABSTRACT
Recent large-scale data sets of protein complex purifications have provided unprecedented insights into the organization of cellular protein complexes. Several computational methods have been developed to detect co-complexed proteins in these data sets. Their common aim is the identification of biologically relevant protein complexes. However, much less is known about the network of direct physical protein contacts within the detected protein complexes. Therefore, our work investigates whether direct physical contacts can be computationally derived by combining raw data of large-scale protein complex purifications. We assess four established scoring schemes and introduce a new scoring approach that is specifically devised to infer direct physical protein contacts from protein complex purifications. The physical contacts identified by the five methods are comprehensively benchmarked against different reference sets that provide evidence for true physical contacts. Our results show that raw purification data can indeed be exploited to determine high-confidence physical protein contacts within protein complexes. In particular, our new method outperforms competing approaches at discovering physical contacts involving proteins that have been screened multiple times in purification experiments. It also excels in the analysis of recent protein purification screens of molecular chaperones and protein kinases. In contrast to previous findings, we observe that physical contacts inferred from purification experiments of protein complexes can be qualitatively comparable to binary protein interactions measured by experimental high-throughput assays such as yeast two-hybrid. This suggests that computationally derived physical contacts might complement binary protein interaction assays and guide large-scale interactome mapping projects by prioritizing putative physical contacts for further experimental screens.

Show MeSH
All physical contacts involving molecular yeast chaperones extracted from the overall top 3000 physical contacts as inferred by the ISA score. Nodes and edges denote proteins present in the Large-Scale data set and their inferred physical contacts, respectively. The size of a node corresponds to its degree, that is, the number of physical contacts it is involved with. Chaperones are colored in white, whereas proteins with known chaperone-related function, such as cochaperones, are colored in gray. Black nodes denote putative substrates of chaperones. Proteins belonging to known families or assemblies are grouped in gray rectangles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3108834&req=5

Figure 5: All physical contacts involving molecular yeast chaperones extracted from the overall top 3000 physical contacts as inferred by the ISA score. Nodes and edges denote proteins present in the Large-Scale data set and their inferred physical contacts, respectively. The size of a node corresponds to its degree, that is, the number of physical contacts it is involved with. Chaperones are colored in white, whereas proteins with known chaperone-related function, such as cochaperones, are colored in gray. Black nodes denote putative substrates of chaperones. Proteins belonging to known families or assemblies are grouped in gray rectangles.

Mentions: To obtain a more detailed view on the relationships between molecular chaperones and their cofactors, we generated an interaction network induced by the top 3,000 physical contacts as inferred by the ISA method (see Fig. 1A). From this network, we extracted all physical contacts that involve at least one molecular chaperone. The resulting interaction network is displayed in Fig. 5. It contains 79 inferred physical contacts involving 31 of the 63 known yeast chaperones as well as their cofactors and putative substrates.


Inferring physical protein contacts from large-scale purification data of protein complexes.

Schelhorn SE, Mestre J, Albrecht M, Zotenko E - Mol. Cell Proteomics (2011)

All physical contacts involving molecular yeast chaperones extracted from the overall top 3000 physical contacts as inferred by the ISA score. Nodes and edges denote proteins present in the Large-Scale data set and their inferred physical contacts, respectively. The size of a node corresponds to its degree, that is, the number of physical contacts it is involved with. Chaperones are colored in white, whereas proteins with known chaperone-related function, such as cochaperones, are colored in gray. Black nodes denote putative substrates of chaperones. Proteins belonging to known families or assemblies are grouped in gray rectangles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108834&req=5

Figure 5: All physical contacts involving molecular yeast chaperones extracted from the overall top 3000 physical contacts as inferred by the ISA score. Nodes and edges denote proteins present in the Large-Scale data set and their inferred physical contacts, respectively. The size of a node corresponds to its degree, that is, the number of physical contacts it is involved with. Chaperones are colored in white, whereas proteins with known chaperone-related function, such as cochaperones, are colored in gray. Black nodes denote putative substrates of chaperones. Proteins belonging to known families or assemblies are grouped in gray rectangles.
Mentions: To obtain a more detailed view on the relationships between molecular chaperones and their cofactors, we generated an interaction network induced by the top 3,000 physical contacts as inferred by the ISA method (see Fig. 1A). From this network, we extracted all physical contacts that involve at least one molecular chaperone. The resulting interaction network is displayed in Fig. 5. It contains 79 inferred physical contacts involving 31 of the 63 known yeast chaperones as well as their cofactors and putative substrates.

Bottom Line: Our results show that raw purification data can indeed be exploited to determine high-confidence physical protein contacts within protein complexes.In contrast to previous findings, we observe that physical contacts inferred from purification experiments of protein complexes can be qualitatively comparable to binary protein interactions measured by experimental high-throughput assays such as yeast two-hybrid.This suggests that computationally derived physical contacts might complement binary protein interaction assays and guide large-scale interactome mapping projects by prioritizing putative physical contacts for further experimental screens.

View Article: PubMed Central - PubMed

Affiliation: Max Planck Institute for Informatics, Saarbr├╝cken, Germany. sven@mpi-inf.mpg.de

ABSTRACT
Recent large-scale data sets of protein complex purifications have provided unprecedented insights into the organization of cellular protein complexes. Several computational methods have been developed to detect co-complexed proteins in these data sets. Their common aim is the identification of biologically relevant protein complexes. However, much less is known about the network of direct physical protein contacts within the detected protein complexes. Therefore, our work investigates whether direct physical contacts can be computationally derived by combining raw data of large-scale protein complex purifications. We assess four established scoring schemes and introduce a new scoring approach that is specifically devised to infer direct physical protein contacts from protein complex purifications. The physical contacts identified by the five methods are comprehensively benchmarked against different reference sets that provide evidence for true physical contacts. Our results show that raw purification data can indeed be exploited to determine high-confidence physical protein contacts within protein complexes. In particular, our new method outperforms competing approaches at discovering physical contacts involving proteins that have been screened multiple times in purification experiments. It also excels in the analysis of recent protein purification screens of molecular chaperones and protein kinases. In contrast to previous findings, we observe that physical contacts inferred from purification experiments of protein complexes can be qualitatively comparable to binary protein interactions measured by experimental high-throughput assays such as yeast two-hybrid. This suggests that computationally derived physical contacts might complement binary protein interaction assays and guide large-scale interactome mapping projects by prioritizing putative physical contacts for further experimental screens.

Show MeSH