Tandem Repeats in Proteins: Prediction Algorithms and Biological Role

Abstract

Tandem repetitions in protein sequence and structure is a fascinating subject of research which has been a focus of study since the late 1990s. In this survey, we give an overview on the multi-faceted aspects of research on protein tandem repeats (PTR for short), including prediction algorithms, databases, early classification efforts, mechanisms of PTR formation and evolution, and synthetic PTR design. We also touch on the rather open issue of the relationship between PTR and flexibility (or disorder) in proteins. Detection of PTR either from protein sequence or structure data is challenging due to inherent high (biological) signal-to-noise ratio that is a key feature of this problem. As early in silico analytic tools have been key enablers for starting this field of study, we expect that current and future algorithmic and statistical breakthroughs will have a high impact on the investigations of the biological role of PTR.

Positive and strongly relaxed purifying selection drive the evolution of repeats in proteins

“…Numerous algorithms for repeat detection have been developed39. However, because repeats manifest rich patterns of recurrence, divergence and variable lengths, a single uniform detection methodology does not appear to be attainable, and each algorithm is tuned to identify specific patterns of the repetitive phenomena40.…”

WEB-server for search of a periodicity in amino acid and nucleotide sequences

“…In this case, it is possible to find more and more diffused tandem repeats, where such repeats could not be identified at present time [4]. As of today, the developed multiple alignment methods used to search for tandem repeats employ sequences pair comparison to construct multiple alignments [2]. This is connected to the fact that the solution of the problem of creating multiple alignments (number of sequences counting to several dozen and having the length of more than 100 amino acids or nucleotides) using the dynamic programming methods appears to be an NP complete problem and requires computer resources for its solution unattainable at the present moment.…”

“…Only in this case, sequences for multiple alignments are arranged in tandem in a singular amino acid or nucleotide sequence. A large number of mathematical algorithms and methods for finding tandem repeats using the multiple alignments were developed [2,3]. The problem, however, is to learn how to construct multiple alignments for less and less similar to each other sequences (for example, with the number of random replacements of more than 1.5 per a singular amino acid or nucleotide).…”

Search of Fuzzy Periods in the Works of Poetry of Different Authors

“…All these techniques are used to construct the multiple alignment of periods; and they are based either on performing the pairwise alignment of periods, followed by the subsequent creation of a guide tree, or on the search for embryos or common words in periods. Thereafter, the initial multiple alignment of periods is provided; and the optimization thereof is carried out in one way or another, including the use of hidden Markov models, iterative procedures, and some other techniques [10][11][12]. However, all the developed approaches do not ensure construction of the multiple alignment, if the statistically significant pair alignment is missing in the analyzed sequences.…”

“…As of today, there are mathematical approaches based on dynamic programming that allow the accurate identification of fuzzy periods of time series or character sequence in the presence of characters insertion or deletion [9,10]. All these techniques are used to construct the multiple alignment of periods; and they are based either on performing the pairwise alignment of periods, followed by the subsequent creation of a guide tree, or on the search for embryos or common words in periods.…”