Albert Chan

PIPE: a protein-protein interaction prediction engine based on the re-occurring short polypeptide sequences between known interacting protein pairs

BackgroundIdentification of protein interaction networks has received considerable attention in the post-genomic era. The currently available biochemical approaches used to detect protein-protein interactions are all time and labour intensive. Consequently there is a growing need for the development of computational tools that are capable of effectively identifying such interactions.ResultsHere we explain the development and implementation of a novel Protein-Protein Interaction Prediction Engine termed PIPE. This tool is capable of predicting protein-protein interactions for any target pair of the yeast Saccharomyces cerevisiae proteins from their primary structure and without the need for any additional information or predictions about the proteins. PIPE showed a sensitivity of 61% for detecting any yeast protein interaction with 89% specificity and an overall accuracy of 75%. This rate of success is comparable to those associated with the most commonly used biochemical techniques. Using PIPE, we identified a novel interaction between YGL227W (vid30) and YMR135C (gid8) yeast proteins. This lead us to the identification of a novel yeast complex that here we term vid30 complex (vid30c). The observed interaction was confirmed by tandem affinity purification (TAP tag), verifying the ability of PIPE to predict novel protein-protein interactions. We then used PIPE analysis to investigate the internal architecture of vid30c. It appeared from PIPE analysis that vid30c may consist of a core and a secondary component. Generation of yeast gene deletion strains combined with TAP tagging analysis indicated that the deletion of a member of the core component interfered with the formation of vid30c, however, deletion of a member of the secondary component had little effect (if any) on the formation of vid30c. Also, PIPE can be used to analyse yeast proteins for which TAP tagging fails, thereby allowing us to predict protein interactions that are not included in genome-wide yeast TAP tagging projects.ConclusionPIPE analysis can predict yeast protein-protein interactions. Also, PIPE analysis can be used to study the internal architecture of yeast protein complexes. The data also suggests that a finite set of short polypeptide signals seem to be responsible for the majority of the yeast protein-protein interactions.

Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences

Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of ∼99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of ∼2 × 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.

CGMGRAPH/CGMLIB: Implementing and Testing CGM Graph Algorithms on PC Clusters and Shared Memory Machines

In this paper, we present CGMgraph, the first integrated library of parallel graph methods for PC clusters based on Coarse Grained Multicomputer (CGM) algorithms. CGMgraph implements parallel methods for various graph problems. Our implementations of deterministic list ranking, Euler tour, connected components, spanning forest, and bipartite graph detection are, to our knowledge, the first efficient implementations for PC clusters. Our library also includes CGMlib, a library of basic CGM tools such as sorting, prefix sum, one-to-all broadcast, all-to-one gather, h-Relation, all-to-all broadcast, array balancing, and CGM partitioning. Both libraries are available for download at http://www.scs.carleton.ca/~cgm. In the experimental part of this paper, we demonstrate the performance of our methods on four different architectures: a gigabit connected high performance PC cluster, a smaller PC cluster connected via fast ethernet, a network of workstations, and a shared memory machine. Our experiments show that our library provides good parallel speedup and scalability on all four platforms. The communication overhead is, in most cases, small and does not grow significantly with an increasing number of processors. This is a very important feature of CGM algorithms which makes them very efficient in practice.

A NOTE ON COARSE GRAINED PARALLEL INTEGER SORTING

We observe that for n/p ≥ p, which is usually the case in practice, there exists a very simple, deterministic, optimal coarse grained parallel integer sorting algorithm with 24 communication rounds (6 n/p-relations and 18 (p-relations), O(n/p) memory per processor and O(n/p) local computation. Experimental data indicates that the algorithm has very good performance in practice.

CGMgraph/CGMlib: Implementing and Testing CGM Graph Algorithms on PC Clusters

In this paper, we present CGMgraph, the first integrated library of parallel graph methods for PC clusters based on CGM algorithms. CGMgraph implements parallel methods for various graph problems. Our implementations of deterministic list ranking, Euler tour, connected components, spanning forest, and bipartite graph detection are, to our knowledge, the first efficient implementations for PC clusters. Our library also includes CGMlib, a library of basic CGM tools such as sorting, prefix sum, one to all broadcast, all to one gather, h-Relation, all to all broadcast, array balancing, and CGM partitioning. Both libraries are available for download at http://cgm.dehne.net.

Coarse grained parallel algorithms for graph matching

Parallel graph algorithm design is a very well studied topic. Many results have been presented for the PRAM model. However, these algorithms are inherently fine grained and experiments show that PRAM algorithms do often not achieve the expected speedup on real machines because of large message overheads. In this paper, we present coarse grained parallel graph algorithms with small message overheads that solve the following standard graph problems related to graph matching: finding maximum matchings in convex bipartite graphs, and finding maximum weight matchings in trees. To our knowledge, these are the first efficient parallel algorithms for these problems that are designed for standard commercial parallel machines such as off-the-shelf processor clusters.

Coarse grained parallel maximum matching in convex bipartite graphs

We present a coarse grained parallel algorithm for computing a maximum matching in a convex bipartite graph G=(A,B,E). For p processors with N/p memory per processor, N=|A|+|B|,N/p/spl ges/p, the algorithm requires O(log p) communication rounds and O(T/sub sequ/(n/p,m/p)+n/p log p) local computation, where n=|A|,m=|B| and T/sub sequ/(n,m) is the sequential time complexity for the problem. For the BSP model, this implies O(log p) supersteps with O(gN+gn/p log p) communication cost and O(T/sub sequ/(n/p,m/p)+n/p log p) local computation.

Coarse grained parallel next element search

The authors present a parallel algorithm for solving the next element search problem on a set of line segments, using a BSP like model referred to as the coarse grained multicomputer (CGM). The algorithm requires O(1) communication rounds (h-relations with h=O(n/p)), O((n/p) log n) local computation, and O((n/p) log n) storage per processor. The result implies solutions to the point location, trapezoidal decomposition and polygon triangulation problems. A simplified version for axis parallel segments requires only O(n/p) storage per processor, and they discuss an implementation of this version. As in a previous paper by Develliers and Fabri (1993), their algorithm is based on a distributed implementation of segment trees which are of size O(n log n). The paper improves on the work of Develliers and Fabri which presented a CGM algorithm for the special case of trapezoidal decomposition only and requires O((n/p)*log p*log n) local computation.

Coarse-Grained Parallel Geometric Search

We present a parallel algorithm for solving thenext element search problemon a set of line segments, using a BSP-like model referred to as thecoarse grained multicomputer(CGM). The algorithm requiresO(1) communication rounds (h-relations withh=O(n/p)),O((n/p)logn) local computation, andO((n/p)logp) memory per processor, assumingn/p?p. Our result implies solutions to the point location, trapezoidal decomposition, and polygon triangulation problems. A simplified version for axis-parallel segments requires onlyO(n/p) memory per processor, and we discuss an implementation of this version. As in a previous paper by Develliers and Fabri (Int. J. Comput. Geom. Appl.6(1996), 487?506), our algorithm is based on a distributed implementation of segment trees which are of sizeO(nlogn). This paper improves onop. cit.in several ways: (1) It studies the more general next element search problem which also solves, e.g., planar point location. (2) The algorithms require onlyO((n/p)logn) local computation instead ofO(logp*(n/p)logn). (3) The algorithms require onlyO((n/p)logp) local memory instead ofO((n/p)logn).

Coarse Grained Parallel Algorithms for Detecting Convex Bipartite Graphs

In this paper, we present parallel algorithms for the coarse grained multicomputer (CGM) and the bulk synchronous parallel computer (BSP) for solving two well known graph problems: (1) determining whether a graph G is bipartite, and (2) determining whether a bipartite graph G is convex. Our algorithms require O(log p) and O(log2 p) communication rounds, respectively, and linear sequential work per round on a CGM with p processors and N/p local memory per processor, N=|G|. The algorithms assume that N/p ≥ pƐ for some fixed Ɛ > 0, which is true for all commercially available multiprocessors. Our results imply BSP algorithms with O(log p) and O(log2 p) supersteps, respectively, O(g log(p)N/p) communication time, and O(log(p)N/p) local computation time. Our algorithm for determining whether a bipartite graph is convex includes a novel, coarse grained parallel, version of the PQ tree data structure introduced by Booth and Lueker. Hence, our algorithm also solves, with the same time complexity as indicated above, the problem of testing the consecutive-ones property for (0, 1) matrices as well as the chordal graph recognition problem. These, in turn, have numerous applications in graph theory, DNA sequence assembly, database theory, and other areas.