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Small sets of interacting proteins suggest functional linkage mechanisms via Bayesian analogical reasoning.

Airoldi EM, Heller KA, Silva R - Bioinformatics (2011)

Bottom Line: Our approach is scalable and can be applied to large databases with minimal computational overhead.Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery.Java code is available at: www.gatsby.ucl.ac.uk/~rbas. airoldi@fas.harvard.edu; kheller@mit.edu; ricardo@stats.ucl.ac.uk.

View Article: PubMed Central - PubMed

Affiliation: Department of Statistics and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. airoldi@fas.harvard.edu

ABSTRACT

Motivation: Proteins and protein complexes coordinate their activity to execute cellular functions. In a number of experimental settings, including synthetic genetic arrays, genetic perturbations and RNAi screens, scientists identify a small set of protein interactions of interest. A working hypothesis is often that these interactions are the observable phenotypes of some functional process, which is not directly observable. Confirmatory analysis requires finding other pairs of proteins whose interaction may be additional phenotypical evidence about the same functional process. Extant methods for finding additional protein interactions rely heavily on the information in the newly identified set of interactions. For instance, these methods leverage the attributes of the individual proteins directly, in a supervised setting, in order to find relevant protein pairs. A small set of protein interactions provides a small sample to train parameters of prediction methods, thus leading to low confidence.

Results: We develop RBSets, a computational approach to ranking protein interactions rooted in analogical reasoning; that is, the ability to learn and generalize relations between objects. Our approach is tailored to situations where the training set of protein interactions is small, and leverages the attributes of the individual proteins indirectly, in a Bayesian ranking setting that is perhaps closest to propensity scoring in mathematical psychology. We find that RBSets leads to good performance in identifying additional interactions starting from a small evidence set of interacting proteins, for which an underlying biological logic in terms of functional processes and signaling pathways can be established with some confidence. Our approach is scalable and can be applied to large databases with minimal computational overhead. Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery.

Availability: Java code is available at: www.gatsby.ucl.ac.uk/~rbas.

Contact: airoldi@fas.harvard.edu; kheller@mit.edu; ricardo@stats.ucl.ac.uk.

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Related in: MedlinePlus

Example with words.
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Figure 1: Example with words.

Mentions: As an intuitive illustration, consider university admission exams, like the American Scholastic Assessment Test (SAT) and Graduate Record Exam (GRE). These exams used to include a section on analogical reasoning. A prototypical analogical reasoning question is shown in Figure 1. The examinee has to answer which of the 5 pairs best matches the relation implicit in DOCTOR:HOSPITAL. Although all candidate pairs interact in some way, pair professor:college seems to best capture the notion of (object, place of work) implicit in the relation between doctor and hospital.Fig. 1.


Small sets of interacting proteins suggest functional linkage mechanisms via Bayesian analogical reasoning.

Airoldi EM, Heller KA, Silva R - Bioinformatics (2011)

Example with words.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117334&req=5

Figure 1: Example with words.
Mentions: As an intuitive illustration, consider university admission exams, like the American Scholastic Assessment Test (SAT) and Graduate Record Exam (GRE). These exams used to include a section on analogical reasoning. A prototypical analogical reasoning question is shown in Figure 1. The examinee has to answer which of the 5 pairs best matches the relation implicit in DOCTOR:HOSPITAL. Although all candidate pairs interact in some way, pair professor:college seems to best capture the notion of (object, place of work) implicit in the relation between doctor and hospital.Fig. 1.

Bottom Line: Our approach is scalable and can be applied to large databases with minimal computational overhead.Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery.Java code is available at: www.gatsby.ucl.ac.uk/~rbas. airoldi@fas.harvard.edu; kheller@mit.edu; ricardo@stats.ucl.ac.uk.

View Article: PubMed Central - PubMed

Affiliation: Department of Statistics and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA. airoldi@fas.harvard.edu

ABSTRACT

Motivation: Proteins and protein complexes coordinate their activity to execute cellular functions. In a number of experimental settings, including synthetic genetic arrays, genetic perturbations and RNAi screens, scientists identify a small set of protein interactions of interest. A working hypothesis is often that these interactions are the observable phenotypes of some functional process, which is not directly observable. Confirmatory analysis requires finding other pairs of proteins whose interaction may be additional phenotypical evidence about the same functional process. Extant methods for finding additional protein interactions rely heavily on the information in the newly identified set of interactions. For instance, these methods leverage the attributes of the individual proteins directly, in a supervised setting, in order to find relevant protein pairs. A small set of protein interactions provides a small sample to train parameters of prediction methods, thus leading to low confidence.

Results: We develop RBSets, a computational approach to ranking protein interactions rooted in analogical reasoning; that is, the ability to learn and generalize relations between objects. Our approach is tailored to situations where the training set of protein interactions is small, and leverages the attributes of the individual proteins indirectly, in a Bayesian ranking setting that is perhaps closest to propensity scoring in mathematical psychology. We find that RBSets leads to good performance in identifying additional interactions starting from a small evidence set of interacting proteins, for which an underlying biological logic in terms of functional processes and signaling pathways can be established with some confidence. Our approach is scalable and can be applied to large databases with minimal computational overhead. Our results suggest that analogical reasoning within a Bayesian ranking problem is a promising new approach for real-time biological discovery.

Availability: Java code is available at: www.gatsby.ucl.ac.uk/~rbas.

Contact: airoldi@fas.harvard.edu; kheller@mit.edu; ricardo@stats.ucl.ac.uk.

Show MeSH
Related in: MedlinePlus