Training-free Measures Based on Algorithmic Probability Identify High Nucleosome Occupancy in DNA Sequences

We introduce and study a set of training-free methods of information-theoretic and algorithmic complexity nature applied to DNA sequences to identify their potential capabilities to determine nucleosomal binding sites. We test our measures on well-studied genomic sequences of different sizes drawn from different sources. The measures reveal the known in vivo versus in vitro predictive discrepancies and uncover their potential to pinpoint (high) nucleosome occupancy. We explore different possible signals within and beyond the nucleosome length and find that complexity indices are informative of nucleosome occupancy. We compare against the gold standard (Kaplan model) and find similar and complementary results with the main difference that our sequence complexity approach. For example, for high occupancy, complexity-based scores outperform the Kaplan model for predicting binding representing a significant advancement in predicting the highest nucleosome occupancy following a training-free approach.Comment: 8 pages main text (4 figures), 12 total with Supplementary (1 figure

Selective pressures on genomes in molecular evolution

We describe the evolution of macromolecules as an information transmission process and apply tools from Shannon information theory to it. This allows us to isolate three independent, competing selective pressures that we term compression, transmission, and neutrality selection. The first two affect genome length: the pressure to conserve resources by compressing the code, and the pressure to acquire additional information that improves the channel, increasing the rate of information transmission into each offspring. Noisy transmission channels (replication with mutations) gives rise to a third pressure that acts on the actual encoding of information; it maximizes the fraction of mutations that are neutral with respect to the phenotype. This neutrality selection has important implications for the evolution of evolvability. We demonstrate each selective pressure in experiments with digital organisms.Comment: 16 pages, 3 figures, to be published in J. theor. Biolog

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Background: Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods: We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions. We also used real data from Streptococcus pneumoniae alignments to compare individual core gene trees to a core genome tree. Results: We found that, as expected, maximum likelihood trees from good quality alignments were the most accurate, but also the most computationally intensive. Using less accurate phylogenetic reconstruction methods, we were able to obtain results of comparable accuracy; we found that approximate results can rapidly be obtained using genetic distance based methods. In real data we found that highly conserved core genes, such as those involved in translation, gave an inaccurate tree topology, whereas genes involved in recombination events gave inaccurate branch lengths. We also show a tree-of-trees, relating the results of different phylogenetic reconstructions to each other. Conclusions: We recommend three approaches, depending on requirements for accuracy and computational time. Quicker approaches that do not perform full maximum likelihood optimisation may be useful for many analyses requiring a phylogeny, as generating a high quality input alignment is likely to be the major limiting factor of accurate tree topology. We have publicly released our simulated data and code to enable further comparisons

Compressing DNA sequence databases with coil

Background: Publicly available DNA sequence databases such as GenBank are large, and are growing at an exponential rate. The sheer volume of data being dealt with presents serious storage and data communications problems. Currently, sequence data is usually kept in large "flat files," which are then compressed using standard Lempel-Ziv (gzip) compression – an approach which rarely achieves good compression ratios. While much research has been done on compressing individual DNA sequences, surprisingly little has focused on the compression of entire databases of such sequences. In this study we introduce the sequence database compression software coil. Results: We have designed and implemented a portable software package, coil, for compressing and decompressing DNA sequence databases based on the idea of edit-tree coding. coil is geared towards achieving high compression ratios at the expense of execution time and memory usage during compression – the compression time represents a "one-off investment" whose cost is quickly amortised if the resulting compressed file is transmitted many times. Decompression requires little memory and is extremely fast. We demonstrate a 5% improvement in compression ratio over state-of-the-art general-purpose compression tools for a large GenBank database file containing Expressed Sequence Tag (EST) data. Finally, coil can efficiently encode incremental additions to a sequence database. Conclusion: coil presents a compelling alternative to conventional compression of flat files for the storage and distribution of DNA sequence databases having a narrow distribution of sequence lengths, such as EST data. Increasing compression levels for databases having a wide distribution of sequence lengths is a direction for future work

Data Discovery and Anomaly Detection Using Atypicality: Theory

A central question in the era of 'big data' is what to do with the enormous amount of information. One possibility is to characterize it through statistics, e.g., averages, or classify it using machine learning, in order to understand the general structure of the overall data. The perspective in this paper is the opposite, namely that most of the value in the information in some applications is in the parts that deviate from the average, that are unusual, atypical. We define what we mean by 'atypical' in an axiomatic way as data that can be encoded with fewer bits in itself rather than using the code for the typical data. We show that this definition has good theoretical properties. We then develop an implementation based on universal source coding, and apply this to a number of real world data sets.Comment: 40 page