Screening for unusual matched segments in multiple protein sequences

This paper presents a parallel hybrid genetic algorithm (GA) for solving the sum-of-pairs multiple protein sequence alignment. A new chromosome representation and its corresponding genetic operators are proposed. A multi-population GENITOR-type GA is combined with local search heuristics. It is then extended to run in parallel on a multiprocessor system for speeding up. Experimental results of benchmarks from the BAliBASE show that the proposed method is superior to MSA, OMA, and SAGA methods with regard to quality of solution and running time. It can be used for finding multiple sequence alignment as well as testing cost functions.

An algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure-based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root. The algorithm encoded in STAMP (STructural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases. In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij' provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij' values and thus provide a reproducible resource for studies of residue conservation within structural motifs.

Multiple sequence alignment with the Divide-and-Conquer method.

Alignment of multiple protein or DNA sequences is an important problem in bioinformatics. Previous work has shown that the A* search algorithm can find optimal alignments for up to several sequences, and that a K-group generalization of A* can find approximate alignments for much larger numbers of sequences [T. Ikeda et al. (1999)]. In this paper, we describe the first implementation of K-group A* that uses quasinatural gap costs, the cost model used in practice by biologists. We also introduce a new method for computing gap-opening costs in profile alignment. Our results show that K-group A* can efficiently find optimal or close-to-optimal alignments for small groups of sequences, and, for large numbers of sequences, it can find higher-quality alignments than the widely-used CLUSTAL family of approximate alignment tools. This demonstrates the benefits of A* in aligning large numbers of sequences, as typically compared by biologists, and suggests that K-group A* could become a practical tool for multiple sequence alignment.

Internet computing and grid technologies promise to change the way we tackle complex problems. They will enable large-scale aggregation and sharing of computational, data and other resources across institutional boundaries. And harnessing these new technologies effectively will transform scientific disciplines ranging from high-energy physics to the life sciences. The computational analysis of biological sequences is a kind of computation driven science. Cause the biology data growing quickly and these databases are heterogeneous. We can use the grid system sharing and integrating the heterogeneous biology database. As we know, bioinformatics tools can speed up analysis the large-scale sequence data, especially about sequence alignment. The FASTA is a tool for aligning multiple protein or nucleotide sequences. FASTA which we used is a distributed and parallel version. The software uses a message-passing library called MPl (Message Passing Interface) and runs on distributed workstation clusters as well as on traditional parallel computers. A grid computing environment is proposed and constructed on multiple Linux PC clusters by using Globus Toolkit (GT) and SUN Grid Engine (SGE). The experimental results and performances of the bioinformatics tool using on grid system are also presented in this paper.

BackgroundThe World Health Organization (WHO) report stated that Acinetobacter baumannii had been classified as one of the most important pathogenic bacteria causing nosocomial infection in hospital patients due to multi-drug resistance (MDR). It is vital to find out new bacterial drug targets and annotated their structure and function for the exploration of new anti-bacterial agents. The present study utilized a systematic route to prioritize the potential drug targets that belong to Mur family of Acinetobacter baumannii and identify their homologous proteins using a computational approach such as sequence similarity search, multiple sequence alignment, phylogenetic analysis, protein sequence, and protein structure analysis. ResultsFrom the results of protein sequence analysis of eight Mur family proteins, they divided into three main enzymatic classes namely transferases (MurG, MurA and MraY), ligases (MurC, MurD, MurE, and MurF), and oxidoreductase (MurB). Based on the results of intra-comparative protein sequence analysis and enzymatic classification, we have chosen MurB, MurE, and MurG as the prioritized drug targets from A. baumannii and subjected them for further detailed studies of inter-species comparison. This inter-species comparison help us to explore the sequential and structural properties of homologous proteins in other species and hence, opens a gateway for new target identification and using common inhibitor for different bacterial species caused by various diseases. The pairwise sequence alignment results between A. baumannii’s MurB with A. calcoaceticus’s MurB, A. baumannii’s MurE with A. seifertii’s MurE, and A. baumannii’s MurG with A. pittii’s MurG showed that every group of the proteins are highly similar with each other and they showed sequence identity of 95.7% and sequence similarity of 97.2%. ConclusionTogether with the results of secondary and three-dimensional structure predictions explained that three selected proteins (MurB, MurE, and MurG) from A. baumannii and their related proteins (AcMurB, AsMurE, and ApMurG) belong to mixed αβ class and they are very similar.

The identification of sequence-based protein domains and their boundaries is often a prelude to structure determination. An accurate prediction of disordered regions, secondary structures and low complexity segments of target protein sequences can improve the efficiency of selection in structural genomics and also aid in design of constructs for directed structural biology studies. At the Center for Eukaryotic Structural Genomics (CESG) we have developed DomainView, a web tool to visualize and analyze predicted protein domains, disordered regions, secondary structures and low complexity segments of target protein sequences for selection of experimental protein structure attempts. DomainView consists of a relational database and a web graphical-user interface. The database was developed based on MySQL, which stores data from target protein sequences and their domains, disordered regions, secondary structures and low complexity segments. The program of the web user interface is a Perl CGI script. When a user searches for a target protein sequence, the script displays the combinational information about the domains and other features of that target sequence graphically on a web page by querying the database. The graphical representation for each feature is linked to a web page showing more detailed annotation information or to a new window directly running the corresponding prediction program to show further information about that feature.

Data Mining is the process to extract hidden predictive information from large databases. In Bioinformatics, data mining enables researchers to meet the challenge of mining large amount of biomolecular data to discover real knowledge. Major research efforts done in the area of bioinformatics involves sequence analysis, protein structure prediction and gene finding. Proteins are said to be prominent molecules in our cells. They involve virtually in all cell functions. The activities and functions of proteins can be determined by protein sequence motifs. These protein motifs are identified from the segments of protein sequences. All segments may not be important to produce good motif patterns. The generated sequence segments do not have classes or labels. Hence, unsupervised segment selection technique is adopted to select significant segments. Therefore Singular Value Decomposition (SVD) entropy method is adopted to select significant sequence segments. In this proposed work, weighted K-Means and Adaptive Fuzzy C-Means have been applied to the selected segments to generate granules, since large amount of segments cannot be grouped or clustered as such. Each granules generated by weighted K-Means algorithm are further clustered by using the K-Means algorithm and granules generated by Adaptive Fuzzy C-Means algorithm are clustered by using Weighted K-Means. The two proposed models are compared with K-Means granular computing model. The experimental results show that Adaptive Fuzzy C-Means with Weighted K-Means technique produces better results than K-Means and weighted K-Means granular computing methods.

Selective constraints are revealed in protein multiple sequence and structural alignments as conserved residues and corresponding atomic interactions. These patterns of conservation contain implicit information about underlying protein mechanisms, just as crystalline X‐ray diffraction patterns contain implicit information about a protein's structure. Contrast hierarchical alignment and interaction network (CHAIN) analysis measures and characterizes selective constraints on the basis of co‐conserved patterns and fits mechanistic models to these and other constraints. Just as the quantity and quality of X‐ray diffraction patterns determines how well one can fit an atomic model to the inferred electron density, the quantity and quality of co‐conserved patterns determines how well one can fit possible mechanisms to these inferred constraints. In principle, given sufficient data, biological mechanisms may be identified with high certainty. Nevertheless, even at “low resolution”, this information can prune the possibilities down to a manageable number for further experimental follow‐up.

A basic task in protein analysis is to discover a set of sequence patterns that characterizes the function of a protein family. To address this task, we introduce a synthesized pattern representation called Aligned Pattern (AP) Cluster to discover potential functional segments in protein sequences. We apply our algorithm to identify and display the binding segments for the Cytochrome C. and Ubiquitin protein families. The resulting AP Clusters correspond to protein binding segments that surround the binding residues. When compared to the results from the protein annotation databases, PROSITE and pFam, ours are more efficient in computation and comprehensive in quality. The significance of the AP Cluster is that it is able to capture subtle variations of the binding segments in protein families. It thus could help to reduce time-consuming simulations and experimentation in the protein analysis.KeywordsProtein AnalysisProtein Function IdentificationPattern DiscoveryPattern ClusteringHierarchical ClusteringMotif FindingLocal AlignmentApproximate String Matching

Identification of transmembrane segments in protein sequences is an important issue in the field of bioinformatics. In this study, a method is proposed for linear discrimination between transmembrane and non-transmembrane segments, combining chemical and statistical features of the proteins with higher-order crossings analysis for protein segment classification. The method was tested on human proteins extracted from public available databases and the results have shown a remarkable efficiency of the proposed algorithm to correctly classify the sequence segments under study into two linearly separated classes, for a wide range of transmembrane segment lengths.

Aligning multiple DNA or protein sequences is a fundamental step in the analyses of phylogeny, homology and molecular structure. Heuristic algorithms are applied because optimal multiple sequence alignment is prohibitively expensive. Heuristic alignment algorithms represent a practical trade-off between speed and accuracy, but they can be improved. We present EVALYN (EVolved ALYNments), a novel approach to multiple sequence alignment in which sequences are progressively aligned based on a guide tree optimized by a genetic algorithm. We hypothesize that a genetic algorithm can find better guide trees than traditional, deterministic clustering algorithms. We compare our novel evolutionary approach to CLUSTAL W and find that EVALYN performs consistently and significantly better as measured by a common alignment scoring technique. Additionally, we hypothesize that evolutionary guide tree optimization is inherently efficient and has less time complexity than the commonly-used neighbor-joining algorithm. We present a compelling analysis in support of this scalability hypothesis.

An automatic sequence searching method (ProtEST) is described which constructs multiple protein sequence alignments from protein sequences and translated expressed sequence tags (ESTs). ProtEST is more effective than a simple TBLASTN search of the query against the EST database, as the sequences are automatically clustered, assembled, made non-redundant, checked for sequence errors, translated into protein and then aligned and displayed. A ProtEST search found a non-redundant, translated, error- and length-corrected EST sequence for > 58% of sequences when single sequences from 1407 Pfam-A seed alignments were used as the probe. The average family size of the resulting alignments of translated EST sequences contained > 10 sequences. In a cross-validated test of protein secondary structure prediction, alignments from the new procedure led to an improvement of 3.4% average Q3 prediction accuracy over single sequences. The ProtEST method is available as an Internet World Wide Web service http://barton.ebi.ac.uk/servers/protest.html+ ++ The Wise2 package for protein and genomic comparisons and the ProtESTWise script can be found at http://www.sanger.ac.uk/Software/Wise2 geoff@ebi.ac.uk

Multiple sequence alignment is a scientific tool to assist the study of DNA homology, phylogeny determinations, and conserved motifs identification. Various heuristic MSA methods have been presented to obtain the resulting alignment for multiple sequences. Although these alignment tools are able to align protein, DNA, and RNA sequences successfully, they are not such successful in aligning coding region sequences because the resulting alignments maybe not consistent with practical observations. Therefore, we propose a method, CORAL-M, a heuristic coding regions alignment method for multiple genome sequences, especially for coding regions. CORAL-M adopts a probabilistic filtration model and the local optimal solution to align genome sequences (codon to codon with the wobble mask rule) by the sliding windows and, thus, obtains the near-optimal alignment in linear time. In the experimental results, CORAL-M can be used to find the potential function sites by aligning viral strains of Poliovirus 1–3, Enterovirus 71, and Coxsackievirus 16.

Small ubiquitin-like modifiers (SUMOs) are tiny but important protein regulators involved in orchestrating a broad spectrum of biological processes, either by covalently modifying protein substrates or by noncovalently interacting with other proteins. Here, we report an updated server, GPS-SUMO 2.0, for the prediction of SUMOylation sites and SUMO-interacting motifs (SIMs). For predictor training, we adopted three machine learning algorithms, penalized logistic regression (PLR), a deep neural network (DNN), and a transformer, and used 52404 nonredundant SUMOylation sites in 8262 proteins and 163 SIMs in 102 proteins. To further increase the accuracy of predicting SUMOylation sites, a pretraining model was first constructed using 145545 protein lysine modification sites, followed by transfer learning to fine-tune the model. GPS-SUMO 2.0 exhibited greater accuracy in predicting SUMOylation sites than did other existing tools. For users, one or multiple protein sequences or identifiers can be input, and the prediction results are shown in a tabular list. In addition to the basic statistics, we integrated knowledge from 35 public resources to annotate SUMOylation sites or SIMs. The GPS-SUMO 2.0 server is freely available at https://sumo.biocuckoo.cn/. We believe that GPS-SUMO 2.0 can serve as a useful tool for further analysis of SUMOylation and SUMO interactions.