Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space

The notion of energy landscapes provides conceptual tools for understanding the complexities of protein folding and function. Energy Landscape Theory indicates that it is much easier to find sequences that satisfy the "Principle of Minimal Frustration" when the folded structure is symmetric (Wolynes, P. G. Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14249-14255). Similarly, repeats and structural mosaics may be fundamentally related to landscapes with multiple embedded funnels. Here we present analytical tools to detect and compare structural repetitions in protein molecules. By an exhaustive analysis of the distribution of structural repeats using a robust metric we define those portions of a protein molecule that best describe the overall structure as a tessellation of basic units. The patterns produced by such tessellations provide intuitive representations of the repeating regions and their association towards higher order arrangements. We find that some protein architectures can be described as nearly periodic, while in others clear separations between repetitions exist. Since the method is independent of amino acid sequence information we can identify structural units that can be encoded by a variety of distinct amino acid sequences

De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.

The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) "Linked-Read" technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations

Detecting multineuronal temporal patterns in parallel spike trains

We present a non-parametric and computationally efficient method that detects spatiotemporal firing patterns and pattern sequences in parallel spike trains and tests whether the observed numbers of repeating patterns and sequences on a given timescale are significantly different from those expected by chance. The method is generally applicable and uncovers coordinated activity with arbitrary precision by comparing it to appropriate surrogate data. The analysis of coherent patterns of spatially and temporally distributed spiking activity on various timescales enables the immediate tracking of diverse qualities of coordinated firing related to neuronal state changes and information processing. We apply the method to simulated data and multineuronal recordings from rat visual cortex and show that it reliably discriminates between data sets with random pattern occurrences and with additional exactly repeating spatiotemporal patterns and pattern sequences. Multineuronal cortical spiking activity appears to be precisely coordinated and exhibits a sequential organization beyond the cell assembly concept

A Case Study of the Impact of Musical Pattern Rehearsal on the Acquisition of Oral and Written Language Skills in a Young Child with Learning Differences

The study explores the relationship between learning musical patterns and learning language patterns. A case study of a male diagnosed with learning differences in generative writing and graphic processing indicates a positive relationship between the neurological patterning of rehearsed musical patterns and the acquisition of oral and written language skills. The anecdotal study tracks the development of literacy from the initial identification of dysfunctional patterns of performance at age three through the acquisition of oral language and the mastery of basic reading skills in the primary years. Analysis of the case study supports the need for musical training in the preschool setting as a foundational component of early literacy programs

EasyDIAg: A tool for easy determination of interrater agreement

Reliable measurements are fundamental for the empirical sciences. In observational research, measurements often consist of observers categorizing behavior into nominalscaled units. Since the categorization is the outcome of a complex judgment process, it is important to evaluate the extent to which these judgments are reproducible, by having multiple observers independently rate the same behavior. A challenge in determining interrater agreement for timed-event sequential data is to develop clear objective criteria to determine whether two raters’ judgments relate to the same event (the linking problem). Furthermore, many studies presently report only raw agreement indices, without considering the degree to which agreement can occur by chance alone. Here, we present a novel, free, and open-source toolbox (EasyDIAg) designed to assist researchers with the linking problem, while also providing chance-corrected estimates of interrater agreement. Additional tools are included to facilitate the development of coding schemes and rater training