Doctor of Philosophy from the University of Virginia in 1979, Dr. Howell has treated children, Similarity score is calculated by dividing the number of matches by the sum of all paired residues of the two compared sequences.

Many One of the most widely used tools for searching for motifs is PHI-Blast [43]and Gapped Local Alignments of Motifs (GLAM2) [44]. Chang, C. C. Chen, C. L. Chen, and J. M. Ho, A de novo next generation genomic sequence assembler based on string graph and mapreduce cloud computing framework,, B. Langmead, K. D. Hansen, and J. T. Leek, Cloud-scale RNA-sequencing differential expression analysis with Myrna,, D. Hong, A. Rhie, S.-S. Park et al., FX: an RNA-seq analysis tool on the cloud,, L. Jourdren, M. Bernard, M. A. Dillies, and S. Le Crom, Eoulsan: a cloud computing-based framework facilitating high throughput sequencing analyses,, M. Niemenmaa, A. Kallio, A. Schumacher, P. Klemel, E. Korpelainen, and K. Heljanko, Hadoop-BAM: directly manipulating next generation sequencing data in the cloud,, B. D. O'Connor, B. Merriman, and S. F. Nelson, SeqWare Query Engine: storing and searching sequence data in the cloud,, A. McKenna, M. Hanna, E. Banks et al., The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data,, S. J. Matthews and T. L. Williams, MrsRF: an efficient MapReduce algorithm for analyzing large collections of evolutionary trees,, M. E. Colosimo, M. W. Peterson, S. Mardis, and L. Hirschman, Nephele: genotyping via complete composition vectors and MapReduce,, P. D. Vouzis and N. V. Sahinidis, GPU-BLAST: using graphics processors to accelerate protein sequence alignment,, C.-M. Liu, T. Wong, E. Wu et al., SOAP3: ultra-fast GPU-based parallel alignment tool for short reads,, S. Lewis, A. Csordas, S. Killcoyne et al., Hydra: a scalable proteomic search engine which utilizes the Hadoop distributed computing framework,, A. Matsunaga, M. Tsugawa, and J. Fortes, CloudBLAST: combining MapReduce and virtualization on distributed resources for bioinformatics applications, in, X. Feng, R. Grossman, and L. Stein, PeakRanger: a cloud-enabled peak caller for ChIP-seq data,, L. Zhang, S. Gu, Y. Liu, B. Wang, and F. Azuaje, Gene set analysis in the cloud,, S. Leo, F. Santoni, and G. Zanetti, Biodoop: bioinformatics on hadoop, in, H. Huang, S. Tata, and R. J. Prill, BlueSNP: R package for highly scalable genome-wide association studies using Hadoop clusters,, D. R. Kelley, M. C. Schatz, and S. L. Salzberg, Quake: quality-aware detection and correction of sequencing errors,. T-Coffee, which stands for tree-based consistency objective function for alignment evolution, is an iterative MSA algorithm. A progressive alignment is then constructed following the order of the guide tree. The Benefits Of Data Center Virtualization For Businesses, CloudTweaks, 2013. Clustal Omega uses the UPGMA method for sequence guide tree construction. Related software and projects on MapReduce. An improved version of the progressive alignment method was developed called iterative progressive algorithms. These algorithms work in a similar manner to progressive alignment; however, this approach repeatedly applies dynamic programming to realign the initial sequences in order to improve their overall alignment quality, also at the same time adding new sequences to the growing MSA. Cloud computing resources have the potential to aid in solving these problems, by offering a utility model of computing and storage, such as almost unlimited storage capacity, anytime usage, and cheap flexible payment models. . This method aligns two profile hidden Markov models, instead of a profile-profile comparison; this improves the sensitivity and alignment quality significantly. A complete distribution for Apache Hadoop and HBase that includes Hive, Mahout, Pig, Cascading, and many other projects.

Dean and S. Ghemawat, MapReduce: simplified data processing on large clusters,, T. Nguyen, W. Shi, and D. Ruden, CloudAligner: a fast and full-featured MapReduce based tool for sequence mapping,, M. C. Schatz, CloudBurst: highly sensitive read mapping with MapReduce,, L. Pireddu, S. Leo, and G. Zanetti, Seal: a distributed short read mapping and duplicate removal tool,. Clustal Omega uses the k-means++ clustering method by Arthur and Vassilvitskii [50]. Article of the Year Award: Outstanding research contributions of 2021, as selected by our Chief Editors. URL: A parallel read mapping algorithm used for mapping next-generation sequence data to the human genome and other genomes. In order to realise the promise of MSA for large-scale sequence data sets, it is necessary for existing MSA algorithms to be run in a parallelised fashion with the sequence data distributed over a computing cluster or server farm. This proves the theory of parallelization and the use of the cloud computing technologies for improving multiple sequence alignment tools. These scores are computed using the pairwise alignment parameters for DNA and protein sequences. URL: A multipurpose, ultrafast ChIP sequence peak caller. A cloud which is owned and used by a single organisation. The use of cloud platforms also creates new opportunities to make data widely available and share it amongst different research laboratories by uploading data to the cloud. The concept of virtualisation can be applied to devices, servers, operating systems, applications, and networks. VMware Virtualization Software for Desktops, Servers & Virtual Machines for Public and Private Cloud Solutions, 2013. In theory, this method could be extended to more than two sequences; however, in practice, it is too complex, because the time and space complexity becomes very large [17]. Virtualisation is a layered approach for running multiple independent virtual machines (VM) on a single physical machine, sharing the resources yet running on its own operating systems and applications [49]. His lectures on stress reduction, URL: C. Kemena and C. Notredame, Upcoming challenges for multiple sequence alignment methods in the high-throughput era,, R. C. Edgar and S. Batzoglou, Multiple sequence alignment,, C. Notredame, Recent evolutions of multiple sequence alignment algorithms,, G. K. C. O. professional and religious organizations have engaged Dr. Howell to present to them on these and Iterative methods are able to give 5%10% more accurate alignments; however, they are limited to alignments of a few hundred sequences only [21]. was always smaller than Next Generation Apache Hadoop MapReduce Framework. Cloud BioLinux is a publicly accessible Virtual Machine (VM) which offers an on-demand, cloud computing solutions for the bioinformatics field. URL: A support for iterative MapReduce computations. The procedure starts at the tips of the rooted tree proceeding towards the root. . Clustal Omega uses the HHalign package by Johannes Soding 2005 [51] for completing progressive alignments. Cloud computing technologies and concepts are outlined, and the next generation of cloud base MSA algorithms is introduced. The NJ method is often referred to as the star decomposition method [48]. Global optimization is now used on a daily basis, and its application to the MSA problem has become a routine [12]. High performance computing has become very important in large-scale data processing. URL: The common utilities that support the other Hadoop subprojects. URL: A cloud computing pipeline for calculating differential gene expression in large RNA-Seq data sets. ClustalW [24] was introduced by Thompson et al. A new multiple sequence alignment is produced using both the first multiple sequence alignment and the second one. other more specific topics in psychology and spirituality. ClustalW (one of the first members of the Clustal family after ClustalV) is probably the most popular multiple sequence alignment algorithm, being incorporated into a number of so-called black box commercially available bioinformatics packages such DNASTAR, while the recently developed Clustal Omega algorithm is the most accurate and most scalable MSA algorithms currently available. Big data technology algorithms are increasing on monthly bases, facilitating different functional sequence analysis, as outlined in Table 4. MapReduce developed by Google is a general purpose, relatively easy-to-use parallel programming model that is perfect for carrying out analysis of large data sets on commodity hardware clusters. URL: RNA sequence analysis tool for the estimation of gene expression levels and genomic variant calling. The multiple sequence alignment algorithms certainly need to be improved in order to be able to handle large amounts of DNA/RNA/protein sequences and most importantly produce multiple sequence alignments of high quality. The k-means method is a widely used clustering technique which seeks to minimise the average squared distance between points in the same cluster. is complexity, . PaaS also saves time and resources, that is, no need to reinvent the wheel; developers simply build more complex systems using existing platforms. SaaS refers to cloud based delivery of software applications which are hosted by cloud providers. healing, and combating mental illness are sought after by many groups. T-Coffee provides a simple and flexible means of producing multiple sequence alignments by using heterogeneous data sources which are provided to T-Coffee via library of global and local pairwise alignments. If the SP score is improved on the second MSA, then the new alignment is kept and the old is discarded; otherwise, it is deleted and the first alignment is used [20]. A cloud which is shared amongst several users or organizations. Once the distances are computed, the UPGMA method reclusters the sequences producing second guide tree. Up to the mid-1980s, the traditional multiple sequence alignment algorithms were only best suited for two sequences, so when it came to producing multiple sequence alignment with more than two sequences, it was found that completing the alignment manually was faster than using traditional dynamic programming algorithms [16]. Hadoop [94] was initiated by Doug Cutting, who worked on the Apache Nutch project (Hadoop is named after his sons toy, a stuffed yellow elephant). Blastreduce: high performance short read mapping with mapreduce, 2013, B. Langmead, M. C. Schatz, J. Lin, M. Pop, and S. L. Salzberg, Searching for SNPs with cloud computing,, M. C. Schatz, D. Sommer, D. Kelley, and M. Pop, De novo assembly of large genomes using cloud computing, in, Y.-J. The message passing interface (MPI) and graphics processing unit (GPU) are the primal programming APIs for parallel computing. Complexity is of increasing relevance as a result of the increasing number of sequences needed to be aligned.

Computational complexity refers to the time, memory, and CPU requirements. This process produces an initial multiple sequence alignment. The process is completed when two nodes remain separated by a single branch. Finally, the multiple sequence alignment is produced using the HHalign package, which aligns two profile hidden Markov models (HMM) as shown in Figure 2. A parallel short DNA sequence read mapping algorithm optimized for aligning sequence data for use in SNP discovery, genotyping, and personal genomics. URL: A MapReduce-based application for mapping short reads generated by the next-generation sequencing machines. Combining MSA algorithms with cloud computing technologies is therefore likely to improve the speed, quality, and capability for MSA to handle large numbers of sequences. Amazon Web Services (AWS) is the leading IaaS provider, widely recognized for providing the most reliable, scalable, cost-efficient, and user friendly web infrastructure. The algorithm follows a strategy that is very similar to the standard progressive methods for sequence alignments, such as pairwise distances which are calculated firstly by using k-tuple method adopted from ClustalW. A cloud infrastructure that is owned by a cloud provider, who made resources such as infrastructure, software, and platform available to general public for pay-per-use basis, via Internet. When two nodes are linked, their common ancestral node is added to the tree and the terminal nodes with their respective branches are removed from the tree. Accelerating high-performance computing applications using parallel computing, 2013. Global optimization techniques, developed in applied mathematics and operations research, provide a generic toolbox for solving complex optimization problems. Then, all of the k-tuples between the 2 sequences are located using a hash table. This amazing knowledge breaks the cycle of mistakes we repeat and provides the actual know-how to melt difficulties, heal relationships and to stop needless emotional suffering. UPGMA is a straightforward method of tree construction which uses a sequential clustering algorithm in which local homology between operational taxanomic units (OTUs) is identified in order of similarity. This includes tasks such as editing code, debugging, deployment, and runtime. Also, the distances between two strings are measured using Levenshtein edit distance. The vendors own the applications and the users may pay a subscription fee to access them via a VM, where all the applications are installed, without the necessity for the user to have a physical copy of the software installed on their own device. The cloud can do both, own and store the hardware and the software needed for a user to run their applications or processes. This process continues until only two OTUs remain [20]. The differences between traditional and virtual server models can be seen in Figure 4. A lively and energetic speaker, Dr. Howell is a regionally known workshop and seminar presenter. An example of multiple sequence alignment that is optimized in the cloud is the FASTA algorithm published by Vijaykumar et al. Most genomic sequence projects use short read alignment algorithms such as Maq [45], SOAP [46], and the very fast Bowtie [47] algorithms. Aisling O Driscoll and Dr. Roy D. Sleator are Principal Investigators on ClouDx-i an FP7-PEOPLE-2012-IAPP project. Then progressively more distant groups of sequences are aligned until a global alignment is obtained. What cloud computing really means, 2013. However, more than three sequences of biologically relevant length can be difficult and time consuming to align manually; therefore, computational algorithms are used as a matter of course [2]. Therefore, this area of research is very active, aiming to develop a method which can align thousands of sequences that are lengthy and produce high-quality alignments and in a reasonable time [2, 3]. ClustalW and Clustal Omega are described later, and also a brief description is provided for the T-Coffee, Kalign, Mafft, and MUSCLE multiple sequence alignment algorithms. URL: A tool set used to work with next generation genome sequencing technologies (Illumina, ABI SOLiD, 454) which includes a LIMS, Pipeline, and Query Engine. Also, using cloud platforms would reduce duplication and provide easy reproducibility by making the sequence datasets and computational methods easily available [97]. Unfortunately, constructing accurate multiple sequence alignments is a computationally intense and biologically complex task, and as such, no current MSA tool is likely to generate a biologically perfect result. Parallel, distributed multiple sequence alignments in the cloud is likely our only real means of keeping pace with todays sequence tsunami and will ultimately aid in the discovery of novel genes, entire metabolic pathways, novel proteins and potentially medically valuable end-products from the global metabolome [99]. URL: An infrastructure which allows the use of resources of a computer cluster for running data-parallel programs. Secondly, a simplified scoring system is introduced which reduces CPU time and increases the accuracy of alignments. This study presents an implementation of the FASTA algorithm built on the Hadoop/MapReduce framework and MPP Database. The emulator provides a virtual central processing unit (CPU), network card, and hard disk. Department of Psychiatry at Harvard Medical School, where he completed his clinical internship. A cloud that is a combination of public, community, and private clouds. An example of SaaS used in bioinformatics is Cloud BioLinux, which was developed at the J. Craig Venter Institute. of personality typing and dynamics, which he has studied and taught for twenty years. URL: A scalable software pipeline, which combines Bowtie and SoapsSNP for whole genome resequencing analysis. Popular products such as VMware [57] and KVM [58] provide virtual machines to customers. The tree is then built by linking the least distant pair of nodes.

URL: A scalable, efficient multicore algorithm that uses MapReduce to quickly calculate the all-to-all Robinson-Foulds (RF) distance between large numbers of trees. The closest two sequences on the tree are aligned first using normal dynamic programming method. Due to MSA significance, many MSA algorithms have been developed. The tree is then used to group the sequences together during the multiple sequence alignment process. Google App Engine was first released in 2008 and is used for developing and hosting web applications. PaaS providers allow subscribed users to access the components that are required for the user to develop or operate applications. In the (FFT-NS-2) method, low-quality all-pairwise distances are rapidly calculated, a provisional MSA is constructed, refined distances are calculated from the MSA, and then the second method (FFT-NS-i) is performed. Progressive alignment works by building the full alignment progressively, firstly completing pairwise alignments using methods such as the Needleman-Wunsch algorithm, Smith-Waterman algorithm, k-tuple algorithm [19], or k-mer algorithm [20], and then the sequences are clustered together to show the relationship between them using methods such as mBed and k-means [21]. In this review, multiple sequence alignments are discussed, with a specific focus on the ClustalW and Clustal Omega algorithms. The k-tuple method [19], a fast heuristic best guess method, is used for pairwise alignment of all possible sequence pairs. In the progressive alignment, pairwise alignments are completed first in order to produce a distance matrix. Over years of research and practice, Dr. Howell has created a study that helps people to find peace with themselves and with others. As an often mistakenly used analogy for the Internet or anything online, the cloud is a familiar buzzword. In order to use cloud computing services, one requirement has to be met, which is Internet connection. Read the winning articles. First created by Google in order to process vast amounts of data, MapReduce is a programming model and an implementation for storing and processing large data sets. He is married to Lark Dill Howell and they are the parents of Benton and Lauren. This sets the most likely region for similarity between the two sequences to occur. Until recently, this was not a problem because A suite of distributed applications for aligning, manipulating, and analysing short DNA reads. It should be noted that while cloud computing is a recent technology, some of the concepts behind cloud computing are not new, such as distributed systems, grid computing, and parallelised programming. Microsoft Home Page, Devices and Services, 2013. Fixed penalties for every gap are subtracted from the similarity score with the similarity scores later converted to a distance score by dividing the similarity score by 100 and subtracting it from 1.0 to provide the number of differences per site. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A wide range of computational algorithms have been applied to the MSA problem, including slow, yet accurate, methods like dynamic programming and faster but less accurate heuristic or probabilistic methods. The reason for structure-based MSA being of better quality is not due to a better algorithm but rather an effect of structures evolutionary stability that is, structures evolve more slowly than sequences [39]. mBed works by emBedding each sequence in a space of Such technology provides a scalable and cost-efficient solution to the big data challenge. A Definition of The Cloud at Last?Web Performance Watch, 2013. Additionally, Apache Hadoop is a software framework that implements the distributed processing of big data sets across cluster farms based on the MapReduce model. SaaS providers run and maintain all necessary hardware and software. Also, other popular multiple sequence alignments could possibly be recoded, so it could complete MSA algorithm over a cluster of machines in a distributed, parallelised way by using the Hadoop/MapReduce framework. Cloud computing is an information technology discipline, which provides computing, such as the necessary storage space and processing power, on demand and as a service. ClustalW is a widely used system for aligning any number of homologous nucleotide or protein sequences. Virtualisation is beneficial due to providing easy access to data, the ability to share applications from central environment, and it reduces the cost associated with data backups, maintenance personnel, and software licensing [56]. Using the MapReduce paradigm, the user specifies a map function which analyses data with the reduce function merging all the results associated with the values from the map phase [69]. Multiple sequence alignments can also be constructed by using already existing protein structural information. After the similarity scores are determined from the pairwise alignment, Clustal Omega employs the mBed method which has a complexity of A more precise definition is provided by the National Institute of Standards and Technology (NIST) who describe it as a pay-per-use model of enabling available, convenient and on-demand network access to a shared pool of configurable computing resources that can be rapidly provisioned and released with minimal management effort or service provider interaction [48]. URL: A gene set analysis algorithm for biomarker identification in the cloud. In contrast to the existing methods, what makes this algorithm different is the use of Wu-Manber approximate string-matching algorithm. T-Coffee can only align maximum 100 sequences without loss of accuracy [52]. Next-generation sequencing technologies are changing the biology landscape, flooding the databases with massive amounts of raw sequence data. Cloud 101: What the heck do IaaS, PaaS and SaaS companies do? 2013. element vector. URL: Hadoop Distributed File System is a distributed file system designed to run on commodity hardware. in 2012. reference sequences. These vectors can then be clustered extremely quickly by methods such as k-means or UPGMA [49]. Pairs of OTUs that are most similar are first determined and then are treated as a new single OTU. These methods are used to find motifs in the long sequences; this process is viewed as a needle in a haystack problem, due to the fact that the algorithm looks for a short stretch of amino acids (motif) in the long sequence. Do and K. Katoh, Protein multiple sequence alignment,, R. C. Edgar, MUSCLE: a multiple sequence alignment method with reduced time and space complexity,, S. B. Needleman and C. D. Wunsch, A general method applicable to the search for similarities in the amino acid sequence of two proteins,, T. F. Smith and M. S. Waterman, Identification of common molecular subsequences,, I. M. Wallace, G. Blackshields, and D. G. Higgins, Multiple sequence alignments,, K. Katoh and H. Toh, Recent developments in the MAFFT multiple sequence alignment program,, D.-F. Feng and R. F. Doolittle, Progressive sequence alignment as a prerequisitetto correct phylogenetic trees,, W. J. Wilbur and D. J. Lipman, Rapid similarity searches of nucleic acid and protein data banks,, R. C. Edgar, MUSCLE: multiple sequence alignment with high accuracy and high throughput,, F. Sievers, A. Wilm, D. Dineen et al., Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega,, N. Saitou and M. Nei, The neighbor-joining method: a new method for reconstructing phylogenetic trees,, I. Gronau and S. Moran, Optimal implementations of UPGMA and other common clustering algorithms,, J. D. Thompson, D. G. Higgins, and T. J. Gibson, CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice,, K. Katoh and D. M. Standley, MAFFT multiple sequence alignment software version 7: improvements in performance and usability,, T. Lassmann and E. L. L. Sonnhammer, Kalignan accurate and fast multiple sequence alignment algorithm,, U. Roshan and D. R. Livesay, Probalign: multiple sequence alignment using partition function posterior probabilities,, B. Morgenstern, DIALIGN: multiple DNA and protein sequence alignment at BiBiServ,, A. Lytynoja and N. Goldman, Phylogeny-aware gap placement prevents errors in sequence alignment and evolutionary analysis,, R. K. Bradley, A. Roberts, M. Smoot et al., Fast statistical alignment,, P. Di Tommaso, S. Moretti, I. Xenarios et al., T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension,, C. Notredame, D. G. Higgins, and J. Heringa, T-coffee: a novel method for fast and accurate multiple sequence alignment,, C. B. SaaS eliminates the need to install software locally on computers with the user instead accessing software via the Internet. Salesforce.com does not sell licence for this software, instead it charges a monthly subscription fee starting from $65 per user per month and delivers this software directly to users via Internet [66]. Users have access to a range of preconfigured command line and graphical software applications, documentation, and more than 135 bioinformatics tools for applications such as sequence alignments, clustering, tree construction, editing, and phylogeny. The main concerns with scaling up and producing MSA of large sets of sequences are the computational complexity, the time it takes to produce the alignment and the accuracy of the final alignment. URL: A scalable machine learning and data mining library. A highly scalable, consistent, distributed, and structured multimaster database. This is done in order to align the residues in two sequences. As seen in Figure 5, users maintain significant management capability when it comes to this service model. One such PaaS technology, Hadoop and Map/Reduce, driven by big data, distributes the data over commodity hardware and provides parallelised processing and analytics. The guide tree is next constructed using the UPGMA method. Each sequence is then replaced by an The data from genomic, proteomic, and metagenomic sequencing projects are increasing at exponential rates, providing information for widening the overall insight of genomes and proteins; however, it is also introducing new challenges such as need for increased storage space, higher power computation, and large data analysis. Joseph B. Howell, Ph.D., LLC is a clinical psychologist who practices in Anniston, Alabama. All public datasets in AWS are delivered as services and therefore can be easily integrated into cloud-based applications. URL: A novel library for scalable manipulation of aligned next-generation sequencing data in the Hadoop distributed computing framework. As the protein alignment problem has been studied for several decades, studies have shown considerable progress in improving the accuracy, quality, and speed of multiple alignment tools, with manually refined alignments continuing to provide superior performance to automated algorithms.