Alignment-Free Sequence Comparison: A Systematic Survey From a Machine Learning Perspective.

The encounter of large amounts of biological sequence data generated during the last decades and the algorithmic and hardware improvements have offered the possibility to apply machine learning techniques in bioinformatics. While the machine learning community is aware of the necessity to rigorously distinguish data transformation from data comparison and adopt reasonable combinations thereof, this awareness is often lacking in the field of comparative sequence analysis. With realization of the disadvantages of alignments for sequence comparison, some typical applications use more and more so-called alignment-free approaches. In light of this development, we present a conceptual framework for alignment-free sequence comparison, which highlights the delineation of: 1) the sequence data transformation comprising of adequate mathematical sequence coding and feature generation, from 2) the subsequent (dis-)similarity evaluation of the transformed data by means of problem-specific but mathematically consistent proximity measures. We consider coding to be an information-loss free data transformation in order to get an appropriate representation, whereas feature generation is inevitably information-lossy with the intention to extract just the task-relevant information. This distinction sheds light on the plethora of methods available and assists in identifying suitable methods in machine learning and data analysis to compare the sequences under these premises.

The Resolved Mutual Information Function as a Structural Fingerprint of Biomolecular Sequences for Interpretable Machine Learning Classifiers.

In the present article we propose the application of variants of the mutual information function as characteristic fingerprints of biomolecular sequences for classification analysis. In particular, we consider the resolved mutual information functions based on Shannon-, Rényi-, and Tsallis-entropy. In combination with interpretable machine learning classifier models based on generalized learning vector quantization, a powerful methodology for sequence classification is achieved which allows substantial knowledge extraction in addition to the high classification ability due to the model-inherent robustness. Any potential (slightly) inferior performance of the used classifier is compensated by the additional knowledge provided by interpretable models. This knowledge may assist the user in the analysis and understanding of the used data and considered task. After theoretical justification of the concepts, we demonstrate the approach for various example data sets covering different areas in biomolecular sequence analysis.

Self-assembled monolayers of subphthalocyanines on gold substrates.

A series of dithiolane-substituted subphthalocyanines have been synthesized that can form self-assembled monolayers on gold surfaces, as confirmed by diverse characterization techniques.