Mehmet Deveci

A comparative analysis of biclustering algorithms for gene expression data

The need to analyze high-dimension biological data is driving the development of new data mining methods. Biclustering algorithms have been successfully applied to gene expression data to discover local patterns, in which a subset of genes exhibit similar expression levels over a subset of conditions. However, it is not clear which algorithms are best suited for this task. Many algorithms have been published in the past decade, most of which have been compared only to a small number of algorithms. Surveys and comparisons exist in the literature, but because of the large number and variety of biclustering algorithms, they are quickly outdated. In this article we partially address this problem of evaluating the strengths and weaknesses of existing biclustering methods. We used the BiBench package to compare 12 algorithms, many of which were recently published or have not been extensively studied. The algorithms were tested on a suite of synthetic data sets to measure their performance on data with varying conditions, such as different bicluster models, varying noise, varying numbers of biclusters and overlapping biclusters. The algorithms were also tested on eight large gene expression data sets obtained from the Gene Expression Omnibus. Gene Ontology enrichment analysis was performed on the resulting biclusters, and the best enrichment terms are reported. Our analyses show that the biclustering method and its parameters should be selected based on the desired model, whether that model allows overlapping biclusters, and its robustness to noise. In addition, we observe that the biclustering algorithms capable of finding more than one model are more successful at capturing biologically relevant clusters.

mrSNP: Software to detect SNP effects on microRNA binding

BackgroundMicroRNAs (miRNAs) are short (19-23 nucleotides) non-coding RNAs that bind to sites in the 3’untranslated regions (3’UTR) of a targeted messenger RNA (mRNA). Binding leads to degradation of the transcript or blocked translation resulting in decreased expression of the targeted gene. Single nucleotide polymorphisms (SNPs) have been found in 3’UTRs that disrupt normal miRNA binding or introduce new binding sites and some of these have been associated with disease pathogenesis. This raises the importance of detecting miRNA targets and predicting the possible effects of SNPs on binding sites. In the last decade a number of studies have been conducted to predict the location of miRNA binding sites. However, there have been fewer algorithms published to analyze the effects of SNPs on miRNA binding. Moreover, the existing software has some shortcomings including the requirement for significant manual labor when working with huge lists of SNPs and that algorithms work only for SNPs present in databases such as dbSNP. These limitations become problematic as next-generation sequencing is leading to large numbers of novel variants in 3’UTRs.ResultIn order to overcome these issues, we developed a web-server named mrSNP which predicts the impact of a SNP in a 3’UTR on miRNA binding. The proposed tool reduces the manual labor requirements and allows users to input any SNP that has been identified by any SNP-calling program. In testing the performance of mrSNP on SNPs experimentally validated to affect miRNA binding, mrSNP correctly identified 69% (11/16) of the SNPs disrupting binding.ConclusionsmrSNP is a highly adaptable and performing tool for predicting the effect a 3’UTR SNP will have on miRNA binding. This tool has advantages over existing algorithms because it can assess the effect of novel SNPs on miRNA binding without requiring significant hands on time.

Hypergraph partitioning for multiple communication cost metrics

We investigate hypergraph partitioning-based methods for efficient parallelization of communicating tasks. A good partitioning method should divide the load among the processors as evenly as possible and minimize the inter-processor communication overhead. The total communication volume is the most popular communication overhead metric which is reduced by the existing state-of-the-art hypergraph partitioners. However, other metrics such as the total number of messages, the maximum amount of data transferred by a processor, or a combination of them are equally, if not more, important. Existing hypergraph-based solutions use a two phase approach to minimize such metrics where in each phase, they minimize a different metric, sometimes at the expense of others. We propose a one-phase approach where all the communication cost metrics can be effectively minimized in a multi-objective setting and reductions can be achieved for all metrics together. For an accurate modeling of the maximum volume and the number of messages sent and received by a processor, we propose the use of directed hypergraphs. The directions on hyperedges necessitate revisiting the standard partitioning heuristics. We do so and propose a multi-objective, multi-level hypergraph partitioner called UMPa. The partitioner takes various prioritized communication metrics into account, and optimizes all of them together in the same phase. Compared to the state-of-the-art methods which only minimize the total communication volume, we show on a large number of problem instances that UMPa produces better partitions in terms of several communication metrics. We propose a novel one-phase multiobjective partitioning technique.We propose a directed hypergraph model.We develop a multilevel tool, UMPa, that incorporates the proposed techniques.

Multithreaded Clustering for Multi-level Hypergraph Partitioning

Requirements for efficient parallelization of many complex and irregular applications can be cast as a hyper graph partitioning problem. The current-state-of-the art software libraries that provide tool support for the hyper graph partitioning problem are designed and implemented before the game-changing advancements in multi-core computing. Hence, analyzing the structure of those tools for designing multithreaded versions of the algorithms is a crucial tasks. The most successful partitioning tools are based on the multi-level approach. In this approach, a given hyper graph is coarsened to a much smaller one, a partition is obtained on the the smallest hyper graph, and that partition is projected to the original hyper graph while refining it on the intermediate hyper graphs. The coarsening operation corresponds to clustering the vertices of a hyper graph and is the most time consuming task in a multi-level partitioning tool. We present three efficient multithreaded clustering algorithms which are very suited for multi-level partitioners. We compare their performance with that of the ones currently used in todays hyper graph partitioners. We show on a large number of real life hyper graphs that our implementations, integrated into a commonly used partitioning library PaToH, achieve good speedups without reducing the clustering quality.

Fast and High Quality Topology-Aware Task Mapping

Considering the large number of processors and the size of the interconnection networks on exactable-capable supercomputers, mapping concurrently executable and communicating tasks of an application is complex problem that needs to be dealt with care. For parallel applications, the communication overhead can be a significant bottleneck on scalability. Topology-aware task-mapping methods that map the tasks tithe processors~(i.e., cores) by exploiting the underlying network information are very effective to avoid, or at worst bend, this limitation. We propose novel, efficient, and effective task mapping algorithms employing a graph model. The experiments show that the methods are faster than the existing approaches proposed for the same task, and on 4096 processors, the algorithms improve the communication hops and link contentions by 16% and 32%, respectively, on the average. In addition, they improve the average execution time of a parallel Spiv kernel and a communication-only application by 9% and 14%, respectively.

Multi-Jagged: A Scalable Parallel Spatial Partitioning Algorithm

Geometric partitioning is fast and effective for load-balancing dynamic applications, particularly those requiring geometric locality of data (particle methods, crash simulations). We present, to our knowledge, the first parallel implementation of a multidimensional-jagged geometric partitioner. In contrast to the traditional recursive coordinate bisection algorithm (RCB), which recursively bisects subdomains perpendicular to their longest dimension until the desired number of parts is obtained, our algorithm does recursive multi-section with a given number of parts in each dimension. By computing multiple cut lines concurrently and intelligently deciding when to migrate data while computing the partition, we minimize data movement compared to efficient implementations of recursive bisection. We demonstrate the algorithms scalability and quality relative to the RCB implementation in Zoltan on both real and synthetic datasets. Our experiments show that the proposed algorithm performs and scales better than RCB in terms of run-time without degrading the load balance. Our implementation partitions 24 billion points into 65,536 parts within a few seconds and exhibits near perfect weak scaling up to 6K cores.

GPU accelerated maximum cardinality matching algorithms for bipartite graphs

We design, implement, and evaluate GPU-based algorithms for the maximum cardinality matching problem in bipartite graphs. Such algorithms have a variety of applications in computer science, scientific computing, bioinformatics, and other areas. To the best of our knowledge, ours is the first study which focuses on the GPU implementation of the maximum cardinality matching algorithms. We compare the proposed algorithms with serial and multicore implementations from the literature on a large set of real-life problems where in majority of the cases one of our GPU-accelerated algorithms is demonstrated to be faster than both the sequential and multicore implementations.

Performance-Portable Sparse Matrix-Matrix Multiplication for Many-Core Architectures

We consider the problem of writing performance portablesparse matrix-sparse matrix multiplication (SPGEMM) kernelfor many-core architectures. We approach the SPGEMMkernel from the perspectives of algorithm design and implementation, and its practical usage. First, we design ahierarchical, memory-efficient SPGEMM algorithm. We thendesign and implement thread scalable data structures thatenable us to develop a portable SPGEMM implementation. We show that the method achieves performance portabilityon massively threaded architectures, namely Intels KnightsLanding processors (KNLs) and NVIDIAs Graphic ProcessingUnits (GPUs), by comparing its performance to specializedimplementations. Second, we study an important aspectof SPGEMMs usage in practice by reusing the structure ofinput matrices, and show speedups up to 3× compared to thebest specialized implementation on KNLs. We demonstratethat the portable method outperforms 4 native methods on2 different GPU architectures (up to 17× speedup), and it ishighly thread scalable on KNLs, in which it obtains 101× speedup on 256 threads.

Allele-specific imbalance mapping at human orthologs of mouse susceptibility to colon cancer (Scc) loci.

Colorectal cancer (CRC) can be classified into different types. Chromosomal instable (CIN) colon cancers are thought to be the most common type of colon cancer. The risk of developing a CIN‐related CRC is due in part to inherited risk factors. Genome‐wide association studies have yielded over 40 single nucleotide polymorphisms (SNPs) associated with CRC risk, but these only account for a subset of risk alleles. Some of this missing heritability may be due to gene‐gene interactions. We developed a strategy to identify interacting candidate genes/loci for CRC risk that utilizes both linkage and RNA‐seq data from mouse models in combination with allele‐specific imbalance (ASI) studies in human tumors. We applied our strategy to three previously identified CRC susceptibility loci in the mouse that show evidence of genetic interaction: Scc4, Scc5 and Scc13. 525 SNPs from genes showing differential expression in the mouse and/or a previous role in cancer from the literature were evaluated for allele‐specific imbalance in 194 paired human normal/tumor DNAs from CIN‐related CRCs. One hundred three SNPs showing suggestive evidence of ASI (31 variants with uncorrected p values < 0.05) were genotyped in a validation set of 296 paired DNAs. Two variants in SNX10 (SCC13) showed significant evidence of allelic selection after multiple comparisons testing. Future studies will evaluate the role of these variants in combination with interacting genetic partners in colon cancer risk in mouse and humans.

Querying Co-regulated Genes on Diverse Gene Expression Datasets Via Biclustering.

Rapid development and increasing popularity of gene expression microarrays have resulted in a number of studies on the discovery of co-regulated genes. One important way of discovering such co-regulations is the query-based search since gene co-expressions may indicate a shared role in a biological process. Although there exist promising query-driven search methods adapting clustering, they fail to capture many genes that function in the same biological pathway because microarray datasets are fraught with spurious samples or samples of diverse origin, or the pathways might be regulated under only a subset of samples. On the other hand, a class of clustering algorithms known as biclustering algorithms which simultaneously cluster both the items and their features are useful while analyzing gene expression data, or any data in which items are related in only a subset of their samples. This means that genes need not be related in all samples to be clustered together. Because many genes only interact under specific circumstances, biclustering may recover the relationships that traditional clustering algorithms can easily miss. In this chapter, we briefly summarize the literature using biclustering for querying co-regulated genes. Then we present a novel biclustering approach and evaluate its performance by a thorough experimental analysis.