Saeed Salem

Proteomic and phospho-proteomic profile of human platelets in basal, resting state: insights into integrin signaling.

During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future.

ORIGAMI: Mining Representative Orthogonal Graph Patterns

In this paper, we introduce the concept of alpha-orthogonal patterns to mine a representative set of graph patterns. Intuitively, two graph patterns are alpha-orthogonal if their similarity is bounded above by alpha. Each alpha-orthogonal pattern is also a representative for those patterns that are at least beta similar to it. Given user defined alpha, beta isin [0,1], the goal is to mine an alpha-orthogonal, beta-representative set that minimizes the set of unrepresented patterns. We present ORIGAMI, an effective algorithm for mining the set of representative orthogonal patterns. ORIGAMI first uses a randomized algorithm to randomly traverse the pattern space, seeking previously unexplored regions, to return a set of maximal patterns. ORIGAMI then extracts an alpha-orthogonal, beta-representative set from the mined maximal patterns. We show the effectiveness of our algorithm on a number of real and synthetic datasets. In particular, we show that our method is able to extract high quality patterns even in cases where existing enumerative graph mining methods fail to do so.

Agent-Oriented Designs for a Self Healing Smart Grid

Electrical grids are highly complex and dynamic systems that can be unreliable, insecure, and inefficient in serving end consumers. The promise of Smart Grids lies in the architecting and developing of intelligent distributed and networked systems for automated monitoring and controlling of the grid to improve performance. We have designed an agent-oriented architecture for a simulation which can help in understanding Smart Grid issues and in identifying ways to improve the electrical grid. We focus primarily on the self-healing problem, which concerns methodologies for activating control solutions to take preventative actions or to handle problems after they occur. We present software design issues that must be considered in producing a system that is flexible, adaptable and scalable. Agent-based systems provide a paradigm for conceptualizing, designing, and implementing software systems. Agents are sophisticated computer programs that can act autonomously and communicate with each other across open and distributed environments. We present design issues that are appropriate in developing a Multi-agent System (MAS) for the grid. Our MAS is implemented in the Java Agent Development Framework (JADE). Our Smart Grid Simulation uses many types of agents to acquire and monitor data, support decision making, and represent devices, controls, alternative power sources, the environment, management functions, and user interfaces.

Intrinsically disordered regions in autophagy proteins.

Autophagy is an essential eukaryotic pathway required for cellular homeostasis. Numerous key autophagy effectors and regulators have been identified, but the mechanism by which they carry out their function in autophagy is not fully understood. Our rigorous bioinformatic analysis shows that the majority of key human autophagy proteins include intrinsically disordered regions (IDRs), which are sequences lacking stable secondary and tertiary structure; suggesting that IDRs play an important, yet hitherto uninvestigated, role in autophagy. Available crystal structures corroborate the absence of structure in some of these predicted IDRs. Regions of orthologs equivalent to the IDRs predicted in the human autophagy proteins are poorly conserved, indicating that these regions may have diverse functions in different homologs. We also show that IDRs predicted in human proteins contain several regions predicted to facilitate protein–protein interactions, and delineate the network of proteins that interact with each predicted IDR‐containing autophagy protein, suggesting that many of these interactions may involve IDRs. Lastly, we experimentally show that a BCL2 homology 3 domain (BH3D), within the key autophagy effector BECN1 is an IDR. This BH3D undergoes a dramatic conformational change from coil to α‐helix upon binding to BCL2s, with the C‐terminal half of this BH3D constituting a binding motif, which serves to anchor the interaction of the BH3D to BCL2s. The information presented here will help inform future in‐depth investigations of the biological role and mechanism of IDRs in autophagy proteins. Proteins 2014; 82:565–578.

Robust partitional clustering by outlier and density insensitive seeding

The leading partitional clustering technique, k-means, is one of the most computationally efficient clustering methods. However, it produces a local optimal solution that strongly depends on its initial seeds. Bad initial seeds can also cause the splitting or merging of natural clusters even if the clusters are well separated. In this paper, we propose, ROBIN, a novel method for initial seed selection in k-means types of algorithms. It imposes constraints on the chosen seeds that lead to better clustering when k-means converges. The constraints make the seed selection method insensitive to outliers in the data and also assist it to handle variable density or multi-scale clusters. Furthermore, they (constraints) make the method deterministic, so only one run suffices to obtain good initial seeds, as opposed to traditional random seed selection approaches that need many runs to obtain good seeds that lead to satisfactory clustering. We did a comprehensive evaluation of ROBIN against state-of-the-art seeding methods on a wide range of synthetic and real datasets. We show that ROBIN consistently outperforms existing approaches in terms of the clustering quality.

FlexSnap: Flexible Non-sequential Protein Structure Alignment

BackgroundProteins have evolved subject to energetic selection pressure for stability and flexibility. Structural similarity between proteins that have gone through conformational changes can be captured effectively if flexibility is considered. Topologically unrelated proteins that preserve secondary structure packing interactions can be detected if both flexibility and Sequential permutations are considered. We propose the FlexSnap algorithm for flexible non-topological protein structural alignment.ResultsThe effectiveness of FlexSnap is demonstrated by measuring the agreement of its alignments with manually curated non-sequential structural alignments. FlexSnap showed competitive results against state-of-the-art algorithms, like DALI, SARF2, MultiProt, FlexProt, and FATCAT. Moreover on the DynDom dataset, FlexSnap reported longer alignments with smaller rmsd.ConclusionsWe have introduced FlexSnap, a greedy chaining algorithm that reports both sequential and non-sequential alignments and allows twists (hinges). We assessed the quality of the FlexSnap alignments by measuring its agreements with manually curated non-sequential alignments. On the FlexProt dataset, FlexSnap was competitive to state-of-the-art flexible alignment methods. Moreover, we demonstrated the benefits of introducing hinges by showing significant improvements in the alignments reported by FlexSnap for the structure pairs for which rigid alignment methods reported alignments with either low coverage or large rmsd.AvailabilityAn implementation of the FlexSnap algorithm will be made available online at http://www.cs.rpi.edu/~zaki/software/flexsnap.

An integrated, generic approach to pattern mining: data mining template library

Frequent pattern mining (FPM) is an important data mining paradigm to extract informative patterns like itemsets, sequences, trees, and graphs. However, no practical framework for integrating the FPM tasks has been attempted. In this paper, we describe the design and implementation of the Data Mining Template Library (DMTL) for FPM. DMTL utilizes a generic data mining approach, where all aspects of mining are controlled via a set of properties. It uses a novel pattern property hierarchy to define and mine different pattern types. This property hierarchy can be thought of as a systematic characterization of the pattern space, i.e., a meta-pattern specification that allows the analyst to specify new pattern types, by extending this hierarchy. Furthermore, in DMTL all aspects of mining are controlled by a set of different mining properties. For example, the kind of mining approach to use, the kind of data types and formats to mine over, the kind of back-end storage manager to use, are all specified as a list of properties. This provides tremendous flexibility to customize the toolkit for various applications. Flexibility of the toolkit is exemplified by the ease with which support for a new pattern can be added. Experiments on synthetic and public dataset are conducted to demonstrate the scalability provided by the persistent back-end in the library. DMTL been publicly released as open-source software (http://dmtl.sourceforge.net/), and has been downloaded by numerous researchers from all over the world.

SPARCL: Efficient and Effective Shape-Based Clustering

Clustering is one of the fundamental data mining tasks. Many different clustering paradigms have been developed over the years, which include partitional, hierarchical, mixture model based, density-based, spectral, subspace, and so on. The focus of this paper is on full-dimensional, arbitrary shaped clusters. Existing methods for this problem suffer either in terms of the memory or time complexity (quadratic or even cubic). This shortcoming has restricted these algorithms to datasets of moderate sizes. In this paper we propose SPARCL, a simple and scalable algorithm for finding clusters with arbitrary shapes and sizes, and it has linear space and time complexity. SPARCL consists of two stages - the first stage runs a carefully initialized version of the K-means algorithm to generate many small seed clusters. The second stage iteratively merges the generated clusters to obtain the final shape-based clusters. Experiments were conducted on a variety of datasets to highlight the effectiveness, efficiency, and scalability of our approach. On the large datasets SPARCL is an order of magnitude faster than the best existing approaches.

SPARCL: an effective and efficient algorithm for mining arbitrary shape-based clusters

Clustering is one of the fundamental data mining tasks. Many different clustering paradigms have been developed over the years, which include partitional, hierarchical, mixture model based, density-based, spectral, subspace, and so on. The focus of this paper is on full-dimensional, arbitrary shaped clusters. Existing methods for this problem suffer either in terms of the memory or time complexity (quadratic or even cubic). This shortcoming has restricted these algorithms to datasets of moderate sizes. In this paper we propose SPARCL, a simple and scalable algorithm for finding clusters with arbitrary shapes and sizes, and it has linear space and time complexity. SPARCL consists of two stages—the first stage runs a carefully initialized version of the Kmeans algorithm to generate many small seed clusters. The second stage iteratively merges the generated clusters to obtain the final shape-based clusters. Experiments were conducted on a variety of datasets to highlight the effectiveness, efficiency, and scalability of our approach. On the large datasets SPARCL is an order of magnitude faster than the best existing approaches.

SimClus: an effective algorithm for clustering with a lower bound on similarity

Clustering algorithms generally accept a parameter k from the user, which determines the number of clusters sought. However, in many application domains, like document categorization, social network clustering, and frequent pattern summarization, the proper value of k is difficult to guess. An alternative clustering formulation that does not require k is to impose a lower bound on the similarity between an object and its corresponding cluster representative. Such a formulation chooses exactly one representative for every cluster and minimizes the representative count. It has many additional benefits. For instance, it supports overlapping clusters in a natural way. Moreover, for every cluster, it selects a representative object, which can be effectively used in summarization or semi-supervised classification task. In this work, we propose an algorithm, SimClus, for clustering with lower bound on similarity. It achieves a O(log n) approximation bound on the number of clusters, whereas for the best previous algorithm the bound can be as poor as O(n). Experiments on real and synthetic data sets show that our algorithm produces more than 40% fewer representative objects, yet offers the same or better clustering quality. We also propose a dynamic variant of the algorithm, which can be effectively used in an on-line setting.