MOTIVATION: Over the past decade, there have been impressive advances in determining the 3D structures of protein complexes. However, there are still many complexes with unknown structures, even when the structures of the individual proteins are known. The advent of protein sequence information provides an opportunity to leverage evolutionary information to enhance the accuracy of protein-protein interface prediction. To this end, several statistical and machine learning methods have been proposed. In particular, direct coupling analysis has recently emerged as a promising approach for identification of protein contact maps from sequential information. However, the ability of these methods to detect protein-protein inter-residue contacts remains relatively limited. RESULTS: In this work, we propose a method to integrate sequential and co-evolution information with structural and functional information to increase the performance of protein-protein interface prediction. Further, we present a post-processing clustering method that improves the average relative F1 score by 70% and 24% and the average relative precision by 80% and 36% in comparison with two state-of-the-art methods, PSICOV and GREMLIN. AVAILABILITY AND IMPLEMENTATION: https://github.com/BioMLBoston/PatchDCA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Understanding the nature of many diseases, including cancer, requires locating somatically acquired rearrangements corresponding to large-scale chromosomal aberrations. Computational methods to detect inter-chromosomal rearrangements based on next-generation sequencing platforms face the big challenge of accurately predicting the location of sites spanned by a typically small number of reads, while the entire sample contains hundreds of millions of reads. In this work, we propose a method called TDJD that identifies the location of interchromosomal breakpoints corresponding to a large scale structural variations, in particular translocations and insertions. To reduce the huge dimension of the search space, we split candidate reads that can be potential break points into windows, and represent the windows as a sequence of binary fingerprints. We then search for the location of the breakpoint in the reference genome using Jaccard distance. We use a combination of parallel computing, search using Jaccard distance to solve the exact nearest neighbor problem. The dimensionality reduction takes advantage of an SSE multi-thread architecture to achieve efficient search. We applied our algorithm to identify several reads with breakpoints, including those characterizing the PAX8-PPARγ rearrangement, a frequent modification occurring in follicular thyroid cancer. Our results show that we could identify the breakpoints much faster than the previous method. We also compared our results to several recently published methods, and found that our method is faster than all other compared methods with high accuracy.

Microarray gene expression data comes as a time series, where the expression level of a gene is recorded at specific time points. Comparing the time series produced by two genes can give us information about the regulatory or inhibitory relationship between the genes. We present a Dynamic Programming (DP) method to compare gene expression data using geometric similarity. We aim to detect similarities and relationships between genes, based on their expression time series. By representing the time series as polygons and compare them, we can find relationships that are not available when the two time series are compared point-by-point. We applied our algorithm on a dataset of 343 regulatory pairs from the alpha dataset and compared them to randomly generated pairs. Using an SVM classifier, we find the optimal similarity score that separates the regulatory dataset from the random pairs. Our results show that we can detect similar pairs better than simple Pearson correlation and we outperform many of the existing methods. This method is an ongoing approach, that can be applied to finding the similarity of any data that can convert to 2D polygon. In the future, we plan to introduce this method as a new classifier.

Microarray gene expression data comes as a time series, where the expression level of a gene is recorded at specific time points. Comparing the time series produced by two genes can give us information about the regulatory or inhibitory relationship between the genes. We present a Dynamic Programming (DP) method to compare gene expression data using geometric similarity. We aim to detect similarities and relationships between genes, based on their expression time series. By representing the time series as polygons and compare them, we can find relationships that are not available when the two time series are compared point-by-point. We applied our algorithm on a dataset of 343 regulatory pairs from the alpha dataset and compared them to randomly generated pairs. Using an SVM classifier, we find the optimal similarity score that separates the regulatory dataset from the random pairs. Our results show that we can detect similar pairs better than simple Pearson correlation and we outperform many of the existing methods. This method is an ongoing approach, that can be applied to finding the similarity of any data that can convert to 2D polygon. In the future, we plan to introduce this method as a new classifier.