A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

Abstract

Protein structure and function information is coded in amino acid sequences. However, the relationship between primary sequences and three-dimensional structures and functions remains enigmatic. Our approach to this fundamental biochemistry problem is based on the frequencies of short constituent sequences (SCSs) or words. A protein amino acid sequence is considered analogous to an English sentence, where SCSs are equivalent to words. Availability scores, which are defined as real SCS frequencies in the non-redundant amino acid database relative to their probabilistically expected frequencies, demonstrate the biological usage bias of SCSs. As a result, this frequency-based linguistic approach is expected to have diverse applications, such as secondary structure specifications by structure-specific SCSs and immunological adjuvants with rare or non-existent SCSs. Linguistic similarities (e.g., wide ranges of scale-free distributions) and dissimilarities (e.g., behaviors of low-rank samples) between proteins and the natural English language have been revealed in the rank-frequency relationships of SCSs or words. We have developed a web server, the SCS Package, which contains five applications for analyzing protein sequences based on the linguistic concept. These tools have the potential to assist researchers in deciphering structurally and functionally important protein sites, species-specific sequences, and functional relationships between SCSs. The SCS Package also provides researchers with a tool to construct amino acid sequences de novo based on the idiomatic usage of SCSs.

Search for Human-Specific Proteins Based on Availability Scores of Short Constituent Sequences: Identification of a WRWSH Protein in Human Testis

“…There are some noteworthy recent studies that encourage this line of approach: for example, nonrandom distributions of 5-aa SCS are demonstrated in the current proteome databases [38], confirming the previous finding that biological bias occurs in protein coding [28,29]. Among these existing studies, our approach is operationally one of the simplest, and it emphasizes analogies between languages and protein sequences [32,33]. Encouragingly, linguistic aspects of proteins have been noted in other studies [48,49].…”

“…The advantage of the alignment-free approach is that any collections of proteins can be compared quantitatively. Although various types of alignment-free approaches have been developed [24,25], including our previous attempts to use membrane topology [26] and a self-organizing map [27], the alignment-free approach in the present study is based on the "availability" (frequency bias) of short constituent sequences (SCSs) of amino acids (aa) in proteins [28][29][30][31][32][33]. The length of SCSs can be 2 aa (doublet), 3 aa (triplet), 4 aa (quartet), 5 aa (pentat), and more in a given protein.…”

Idiom networks for short constituent sequences of amino acids

“…The source data for the package have been obtained from the non-redundant amino acid database [5] of the NCBI (National Center for Biotechnology Information). The SCS package provides five applications which utilize the availability scores of SCSs and idioms [3]. This paper defines a network structure of SCS idioms which is called idiom network of SCSs.…”

“…Bioinformatics is a powerful methodology to utilize such data and to prompt biological researches drastically [1]. In our previous works, we developed a web application called the SCS Package based on Short Constituent Sequence (SCS) of amino acid sequences [2], [3], [4]. The SCS package provides various analysis services using the availability score of SCSs.…”

Protein Word Detection using Text Segmentation Techniques

“…They call the short consequent sequences (SCS) present in protein sequences as words and use availability scores to assess the biological usage bias of SCS. Our approach of using MDL for segmentation is interesting in that it does not require prior fixing of word length as in (Motomura et al, 2012), (Motomura et al, 2013).…”