Evaluating deterministic motif significance measures in protein databases

<p>Abstract</p> <p>Background</p> <p>Assessing the outcome of motif mining algorithms is an essential task, as the number of reported motifs can be very large. Significance measures play a central role in automatically ranking those motifs, and therefore alleviating the analysis work. Spotting the most interesting and relevant motifs is then dependent on the choice of the right measures. The combined use of several measures may provide more robust results. However caution has to be taken in order to avoid spurious evaluations.</p> <p>Results</p> <p>From the set of conducted experiments, it was verified that several of the selected significance measures show a very similar behavior in a wide range of situations therefore providing redundant information. Some measures have proved to be more appropriate to rank highly conserved motifs, while others are more appropriate for weakly conserved ones. Support appears as a very important feature to be considered for correct motif ranking. We observed that not all the measures are suitable for situations with poorly balanced class information, like for instance, when positive data is significantly less than negative data. Finally, a visualization scheme was proposed that, when several measures are applied, enables an easy identification of high scoring motifs.</p> <p>Conclusion</p> <p>In this work we have surveyed and categorized 14 significance measures for pattern evaluation. Their ability to rank three types of deterministic motifs was evaluated. Measures were applied in different testing conditions, where relations were identified. This study provides some pertinent insights on the choice of the right set of significance measures for the evaluation of deterministic motifs extracted from protein databases.</p

Efficient Subgraph Similarity Search on Large Probabilistic Graph Databases

Many studies have been conducted on seeking the efficient solution for subgraph similarity search over certain (deterministic) graphs due to its wide application in many fields, including bioinformatics, social network analysis, and Resource Description Framework (RDF) data management. All these works assume that the underlying data are certain. However, in reality, graphs are often noisy and uncertain due to various factors, such as errors in data extraction, inconsistencies in data integration, and privacy preserving purposes. Therefore, in this paper, we study subgraph similarity search on large probabilistic graph databases. Different from previous works assuming that edges in an uncertain graph are independent of each other, we study the uncertain graphs where edges' occurrences are correlated. We formally prove that subgraph similarity search over probabilistic graphs is #P-complete, thus, we employ a filter-and-verify framework to speed up the search. In the filtering phase,we develop tight lower and upper bounds of subgraph similarity probability based on a probabilistic matrix index, PMI. PMI is composed of discriminative subgraph features associated with tight lower and upper bounds of subgraph isomorphism probability. Based on PMI, we can sort out a large number of probabilistic graphs and maximize the pruning capability. During the verification phase, we develop an efficient sampling algorithm to validate the remaining candidates. The efficiency of our proposed solutions has been verified through extensive experiments.Comment: VLDB201

Risk-Averse Matchings over Uncertain Graph Databases

A large number of applications such as querying sensor networks, and analyzing protein-protein interaction (PPI) networks, rely on mining uncertain graph and hypergraph databases. In this work we study the following problem: given an uncertain, weighted (hyper)graph, how can we efficiently find a (hyper)matching with high expected reward, and low risk? This problem naturally arises in the context of several important applications, such as online dating, kidney exchanges, and team formation. We introduce a novel formulation for finding matchings with maximum expected reward and bounded risk under a general model of uncertain weighted (hyper)graphs that we introduce in this work. Our model generalizes probabilistic models used in prior work, and captures both continuous and discrete probability distributions, thus allowing to handle privacy related applications that inject appropriately distributed noise to (hyper)edge weights. Given that our optimization problem is NP-hard, we turn our attention to designing efficient approximation algorithms. For the case of uncertain weighted graphs, we provide a $\frac{1}{3}$-approximation algorithm, and a $\frac{1}{5}$-approximation algorithm with near optimal run time. For the case of uncertain weighted hypergraphs, we provide a $\Omega(\frac{1}{k})$-approximation algorithm, where $k$ is the rank of the hypergraph (i.e., any hyperedge includes at most $k$ nodes), that runs in almost (modulo log factors) linear time. We complement our theoretical results by testing our approximation algorithms on a wide variety of synthetic experiments, where we observe in a controlled setting interesting findings on the trade-off between reward, and risk. We also provide an application of our formulation for providing recommendations of teams that are likely to collaborate, and have high impact.Comment: 25 page

Innovative Algorithms and Evaluation Methods for Biological Motif Finding

Biological motifs are defined as overly recurring sub-patterns in biological systems. Sequence motifs and network motifs are the examples of biological motifs. Due to the wide range of applications, many algorithms and computational tools have been developed for efficient search for biological motifs. Therefore, there are more computationally derived motifs than experimentally validated motifs, and how to validate the biological significance of the ‘candidate motifs’ becomes an important question. Some of sequence motifs are verified by their structural similarities or their functional roles in DNA or protein sequences, and stored in databases. However, biological role of network motifs is still invalidated and currently no databases exist for this purpose. In this thesis, we focus not only on the computational efficiency but also on the biological meanings of the motifs. We provide an efficient way to incorporate biological information with clustering analysis methods: For example, a sparse nonnegative matrix factorization (SNMF) method is used with Chou-Fasman parameters for the protein motif finding. Biological network motifs are searched by various clustering algorithms with Gene ontology (GO) information. Experimental results show that the algorithms perform better than existing algorithms by producing a larger number of high-quality of biological motifs. In addition, we apply biological network motifs for the discovery of essential proteins. Essential proteins are defined as a minimum set of proteins which are vital for development to a fertile adult and in a cellular life in an organism. We design a new centrality algorithm with biological network motifs, named MCGO, and score proteins in a protein-protein interaction (PPI) network to find essential proteins. MCGO is also combined with other centrality measures to predict essential proteins using machine learning techniques. We have three contributions to the study of biological motifs through this thesis; 1) Clustering analysis is efficiently used in this work and biological information is easily integrated with the analysis; 2) We focus more on the biological meanings of motifs by adding biological knowledge in the algorithms and by suggesting biologically related evaluation methods. 3) Biological network motifs are successfully applied to a practical application of prediction of essential proteins

Motif Discovery in Protein Sequences

Biology has become a data‐intensive research field. Coping with the flood of data from the new genome sequencing technologies is a major area of research. The exponential increase in the size of the datasets produced by “next‐generation sequencing” (NGS) poses unique computational challenges. In this context, motif discovery tools are widely used to identify important patterns in the sequences produced. Biological sequence motifs are defined as short, usually fixed length, sequence patterns that may represent important structural or functional features in nucleic acid and protein sequences such as transcription binding sites, splice junctions, active sites, or interaction interfaces. They can occur in an exact or approximate form within a family or a subfamily of sequences. Motif discovery is therefore an important field in bioinformatics, and numerous methods have been developed for the identification of motifs shared by a set of functionally related sequences. This chapter will review the existing motif discovery methods for protein sequences and their ability to discover biologically important features as well as their limitations for the discovery of new motifs. Finally, we will propose new horizons for motif discovery in order to address the short comings of the existent methods

Exploring Patterns of Epigenetic Information With Data Mining Techniques

[Abstract] Data mining, a part of the Knowledge Discovery in Databases process (KDD), is the process of extracting patterns from large data sets by combining methods from statistics and artificial intelligence with database management. Analyses of epigenetic data have evolved towards genome-wide and high-throughput approaches, thus generating great amounts of data for which data mining is essential. Part of these data may contain patterns of epigenetic information which are mitotically and/or meiotically heritable determining gene expression and cellular differentiation, as well as cellular fate. Epigenetic lesions and genetic mutations are acquired by individuals during their life and accumulate with ageing. Both defects, either together or individually, can result in losing control over cell growth and, thus, causing cancer development. Data mining techniques could be then used to extract the previous patterns. This work reviews some of the most important applications of data mining to epigenetics.Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo; 209RT-0366Galicia. Consellería de Economía e Industria; 10SIN105004PRInstituto de Salud Carlos III; RD07/0067/000

Financial Time series: motif discovery and analysis using VALMOD

Motif discovery and analysis in time series data-sets have a wide-range of applications from genomics to finance. In consequence, development and critical evaluation of these algorithms is required with the focus not just detection but rather evaluation and interpretation of overall significance. Our focus here is the specific algorithm, VALMOD, but algorithms in wide use for motif discovery are summarised and briefly compared, as well as typical evaluation methods with strengths. Additionally, Taxonomy diagrams for motif discovery and evaluation techniques are constructed to illustrate the relationship between different approaches as well as inter-dependencies. Finally evaluation measures based upon results obtained from VALMOD analysis of a GBP-USD foreign exchange (F/X) rate data-set are presented, in illustration