Multiple Sequence Alignment (MSA) is a very basic step in the phylogeny analysis of organisms. In MSA, all the sequences under study are aligned together pairwise on the basis of similar regions with in them. The major goal of MSA pairwise alignment is to identify the alignment that maximizes the protein sequence similarity. This is done by seeking an alignment that “maximizes the sum of similarities for all the pair of sequences”, which is called as the ‘Sum-of-scores or SP Score’. The SP Score is the basic of many alignment algorithms.
The most widely used approach for constructing MSA is “Progressive Alignment”, where a set of n proteins are aligned by performing n-1 pairwise alignments of pairs of proteins or pairs of intermediate alignments guided by a phylogeny tree connecting the sequences. A methodology that has been successfully used as an improvement of progressive alignment based on the SP Score is “Consistency-based Scoring”,where the alignment is consistently dependent on the previously obtained alignment, for example, we have 3 sequences namely, A,B, & C ,the pairwise alignment A-B, B-C imply an alignment of A-C which may be different from the directly computed A to C alignment.
Now, the question arises that how much can we rely on the obtained MSA? and how an MSA is validated?
The validation of MSA program typically uses a benchmark data set of reference alignments. An MSA produced by the program is compared with the corresponding reference alignment which gives an accuracy score.
Before 2004, the standard benchmark was BAliBASE ( Benchmark Alignment dataBASE) , a database of manually refined MSAs consisting of high quality documented alignments to identify the strong and weak points of the numerous alignment programs now available.
“Recently, several new benchmark are made available, namely, OXBENCH, PREFAB, SABmark, IRMBASE and a new extended version of BAliBASE.”
Another parameter which is considered as basic in most of the alignment programs is fM Score. It is used to assess the specificity of an alignment tool and identifies the proportion of matched residues predicted that also appears in the reference alignment. Many of the times, it is encountered that some regions of the sequences are alignable and some are not, however, there are usually also intermediate cases , where sequence and structure have been diverged to a point at which homology is not reliably detectable.In such a case, the fM Score , at best, provides a noisy assessment of alignment tool specificity, that becomes increasingly less reliable as one considers sequences of increasing structural divergence.
However, after considering the reference alignments, the accuracy of results is still questionable as the reference alignments generated are of varying quality.
- Multiple sequence alignment
Robert C Edgar1 and Serafim Batzoglou2
- BAliBASE: a benchmark alignment database for the evaluation of multiple alignment programs
Julie D. Thompson, Frédréric Plewniak and Olivier Poch
MOCCA- A New Suite to Model cis- regulatory Elements for Motif Occurrence Combinatorics
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vs_Analysis.py: A Python Script to Analyze Virtual Screening Results of Autodock Vina
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How to search motif pattern in FASTA sequences using Perl hash?
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BETSY: A new backward-chaining expert system for automated development of pipelines in Bioinformatics
Bioinformatics analyses have become long and difficult as it involves a large number of steps implemented for data processing. Bioinformatics pipelines are developed to make this process easier, which on one hand automate a specific analysis, while on the other hand, are still limited for investigative analyses requiring changes to the parameters used in the process. (more…)
Algorithm and workflow of miRDB
As mentioned in the previous article, Micro RNAs (miRNAs) are the short endogenous RNAs (~22 nucleotides) and originate from the non-coding RNAs , produced in single-celled eukaryotes, viruses, plants, and animals . They play significant roles in various biological processes such as degradation of mRNA . Several databases exist storing a large amount of information about miRNAs, one of such databases miRBase  was explained in the previous article, today we will explain the algorithm of miRDB [5,6], another database for miRNA target prediction. (more…)
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Prediction of biochemical reactions catalyzed by enzymes in humans
There are many biological important enzymes which exist in the human body, one of them is Cytochrome P450 (CyP450) enzymes which are mostly considered in drug discovery due to their involvement in the majority (75%) of drug metabolism . Therefore, various in-silico methods have been applied to predict the possible substrates of CyP 450 enzymes [2-4]. Recently, an in-silico model has been developed to predict the potential chemical reactions mediated by the enzymes present in humans including CyP450 enzymes . (more…)
A new high-level Python interface for MD simulation using GROMACS
The roots of the molecular simulation application can be traced back to physics where it was applied to simplified hard-sphere systems . This field of molecular simulation study has gained a lot of interest since then and applied to perform simulations to fold small protein at multi-microsecond scale [2-4], predict functional properties of receptors and to capture the intermediate transitions of the complex , and to study the movement and behavior of ligand in a binding pocket and also to predict interactions between receptors and ligands [6,7]. (more…)
Machine learning in prediction of ageing-related genes/proteins
Ageing has a great impact on human health, when people’s age advance towards 80 years, approximately half of the proteins in the body get damaged through oxidation. The chemical degradations occurring in our body produce energy by the consumed food via oxidation in the presence of oxygen. (more…)
Simulated sequence alignment software: An alternative to MSA benchmarks
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Benchmark databases for multiple sequence alignment: An overview
Multiple sequence alignment (MSA) is a very crucial step in most of the molecular analyses and evolutionary studies. Many MSA programs have been developed so far based on different approaches which attempt to provide optimal alignment with high accuracy. Basic algorithms employed to develop MSA programs include progressive algorithm , iterative-based , and consistency-based algorithm . Some of the programs incorporate several other methods into the process of creating an optimal alignment such as M-COFFEE  and PCMA . (more…)
ab-initio prediction of protein structure: An introduction
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Intrinsically disordered proteins’ predictors and databases: An overview
Intrinsically unstructured proteins (IUPs) are the natively unfolded proteins which must be unfolded or disordered in order to perform their functions. They are commonly referred to as intrinsically disordered proteins (IDPs) and play significant roles in regulating and signaling biological networks . IDPs are also involved in the assembly of signaling complexes and in the dynamic self-assembly of membrane-less nuclear and cytoplasmic organelles . The disordered regions in a protein can be highly conserved among the species in respect of both the composition and the sequence . (more…)
An introduction to the predictors of pathogenic point mutations
Single nucleotide variation is a change in a single nucleotide in a sequence irrespective of the frequency of the variation. Single nucleotide variants (SNVs) play a very important role in causing several diseases such as the tumor, cancer, etc. Many efforts have been made to identify the SNVs which were initially based on identifying non-synonymous mutations in coding regions of the genomes. (more…)
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Role of Information Theory, Chaos Theory, and Linear Algebra and Statistics in the development of alignment-free sequence analysis
Sequence alignment is customary to not only find similar regions among a pair of sequences but also to study the structural, functional and evolutionary relationship between organisms. Many tools have been discovered to achieve the goal of alignment of a pair of sequences, separately for nucleotide sequence and amino acid sequence, BLOSSUM & PAM  are a few to name. (more…)
Bioinformatics Challenges and Advances in RNA interference
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Systems pharmacology and drug development
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