Relationship between global structural parameters and Enzyme Commission hierarchy: Implications for function prediction

In protein databases there is a substantial number of proteins structurally determined but without function annotation. Understanding the relationship between function and structure can be useful to predict function on a large scale. We have analyzed the similarities in global physicochemical parameters for a set of enzymes which were classified according to the four Enzyme Commission (EC) hierarchical levels. Using relevance theory we introduced a distance between proteins in the space of physicochemical characteristics. This was done by minimizing a cost function of the metric tensor built to reflect the EC classification system. Using an unsupervised clustering method on a set of 1025 enzymes, we obtained no relevant clustering formation compatible with EC classification. The distance distributions between enzymes from the same EC group and from different EC groups were compared by histograms. Such analysis was also performed using sequence alignment similarity as a distance. Our results suggest that global structure parameters are not sufficient to segregate enzymes according to EC hierarchy. This indicates that features essential for function are rather local than global. Consequently, methods for predicting function based on global attributes should not obtain high accuracy in main EC classes prediction without relying on similarities between enzymes from training and validation datasets. Furthermore, these results are consistent with a substantial number of studies suggesting that function evolves fundamentally by recruitment, i.e., a same protein motif or fold can be used to perform different enzymatic functions and a few specific amino acids (AAs) are actually responsible for enzyme activity. These essential amino acids should belong to active sites and an effective method for predicting function should be able to recognize them. (C) 2012 Elsevier Ltd. All rights reserved.

Unveiling the relationship between complex networks metrics and word senses

The automatic disambiguation of word senses (i.e., the identification of which of the meanings is used in a given context for a word that has multiple meanings) is essential for such applications as machine translation and information retrieval, and represents a key step for developing the so-called Semantic Web. Humans disambiguate words in a straightforward fashion, but this does not apply to computers. In this paper we address the problem of Word Sense Disambiguation (WSD) by treating texts as complex networks, and show that word senses can be distinguished upon characterizing the local structure around ambiguous words. Our goal was not to obtain the best possible disambiguation system, but we nevertheless found that in half of the cases our approach outperforms traditional shallow methods. We show that the hierarchical connectivity and clustering of words are usually the most relevant features for WSD. The results reported here shed light on the relationship between semantic and structural parameters of complex networks. They also indicate that when combined with traditional techniques the complex network approach may be useful to enhance the discrimination of senses in large texts. Copyright (C) EPLA, 2012