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Summary: Synthetic proteins with high affinity and selectivity for a protein target can be used as research tools, biomarkers, and pharmacological agents, but few methods exist to design such proteins de novo. To this end, the In-Silico Protein Synthesizer (InSiPS) was developed to design synthetic binding proteins (SBPs) that bind pre-determined targets while minimizing off-target interactions. InSiPS is a genetic algorithm that refines a pool of random sequences over hundreds of generations of mutation and selection to produce SBPs with pre-specified binding characteristics. As a proof of concept, we design SBPs against three yeast proteins and demonstrate binding and functional inhibition of two of three targets in vivo. Peptide SPOT arrays confirm binding sites, and a permutation array demonstrates target specificity. Our foundational approach will support the field of de novo design of small binding polypeptide motifs and has robust applicability while offering potential advantages over the limited number of techniques currently available. : Biological Sciences; Bioinformatics; Protein Family Determination Subject Areas: Biological Sciences, Bioinformatics, Protein Family Determination

Interest in the evolution of protein-protein and genetic interaction networks has been rising in recent years, but the lack of large-scale high quality comparative datasets has acted as a barrier. Here, we carried out a comparative analysis of computationally predicted protein-protein interaction (PPI) networks from five closely related yeast species. We used the Protein-protein Interaction Prediction Engine (PIPE), which uses a database of known interactions to make sequence-based PPI predictions, to generate high quality predicted interactomes. Simulated proteomes and corresponding PPI networks were used to provide null expectations for the extent and nature of PPI network evolution. We found strong evidence for conservation of PPIs, with lower than expected levels of change in PPIs for about a quarter of the proteome. Furthermore, we found that changes in predicted PPI networks are poorly predicted by sequence divergence. Our analyses identified a number of functional classes experiencing fewer PPI changes than expected, suggestive of purifying selection on PPIs. Our results demonstrate the added benefit of considering predicted PPI networks when studying the evolution of closely related organisms.

The subtree prune and regraft distance (dSPR) between phylogenetic trees is important both as a general means of comparing phylogenetic tree topologies as well as a measure of lateral gene transfer (LGT). Although there has been extensive study on the computation of dSPR and similar metrics between rooted trees, much less is known about SPR distances for unrooted trees, which often arise in practice when the root is unresolved. We show that unrooted SPR distance computation is NP-Hard and verify which techniques from related work can and cannot be applied. We then present an efficient heuristic algorithm for this problem and benchmark it on a variety of synthetic datasets. Our algorithm computes the exact SPR distance between unrooted tree, and the heuristic element is only with respect to the algorithm’s computation time. Our method is a heuristic version of a fixed parameter tractability (FPT) approach and our experiments indicate that the running time behaves similar to FPT algorithms. For real data sets, our algorithm was able to quickly compute dSPR for the majority of trees that were part of a study of LGT in 144 prokaryotic genomes. Our analysis of its performance, especially with respect to searching and reduction rules, is applicable to computing many related distance measures.

The subtree prune and regraft distance ( d SPR ) between phylogenetic trees is important both as a general means of comparing phylogenetic tree topologies as well as a measure of lateral gene transfer (LGT). Although there has been extensive study on the computation of d SPR and similar metrics between rooted trees, much less is known about SPR distances for unrooted trees , which often arise in practice when the root is unresolved. We show that unrooted SPR distance computation is NP-Hard and verify which techniques from related work can and cannot be applied. We then present an efficient heuristic algorithm for this problem and benchmark it on a variety of synthetic datasets. Our algorithm computes the exact SPR distance between unrooted tree, and the heuristic element is only with respect to the algorithm's computation time. Our method is a heuristic version of a fixed parameter tractability (FPT) approach and our experiments indicate that the running time behaves similar to FPT algorithms. For real data sets, our algorithm was able to quickly compute d SPR for the majority of trees that were part of a study of LGT in 144 prokaryotic genomes. Our analysis of its performance, especially with respect to searching and reduction rules, is applicable to computing many related distance measures.

This paper proposes an efficient algorithm to compress the cubes in the progress of the parallel data cube generation. This low overhead compression mechanism provides block-by-block and record-by-record compression by using tuple difference coding techniques, thereby maximizing the compression ratio and minimizing the decompression penalty at run-time. The experimental results demonstrate that the typical compression ratio is about 30:1 without sacrificing running time. This paper also demonstrates that the compression method is suitable for Hilbert Space Filling Curve, a mechanism widely used in multi-dimensional indexing.

Abstract. External memory (EM) algorithms are designed for large-scale computational problems in which the size of the internal memory of the computer is only a small fraction of the problem size. Typical EM algorithms are specially crafted for the EM situation. In the past, several attempts have been made to relate the large body of work on parallel algorithms to EM, but with limited success. The combination of EM computing, on multiple disks, with multiprocessor parallelism has been posted as a challenge by the ACM Working Group on Storage I/ O for Large-Scale Computing. In this paper we provide a simulation technique which produces efficient parallel EM algorithms from efficient BSP-like parallel algorithms. The techniques obtained can accommodate one or multiple processors on the EM target machine, each with one or more disks, and they also adapt to the disk blocking factor of the target machine. When applied to existing BSP-like algorithms, our simulation technique produces improved parallel EM algorithms for a large number of problems. [ABSTRACT FROM AUTHOR]