Calibration of the head direction network: a role for symmetric angular head velocity cells

Continuous attractor networks require calibration. Computational models of the head direction (HD) system of the rat usually assume that the connections that maintain HD neuron activity are pre-wired and static. Ongoing activity in these models relies on precise continuous attractor dynamics. It is currently unknown how such connections could be so precisely wired, and how accurate calibration is maintained in the face of ongoing noise and perturbation. Our adaptive attractor model of the HD system that uses symmetric angular head velocity (AHV) cells as a training signal shows that the HD system can learn to support stable firing patterns from poorly-performing, unstable starting conditions. The proposed calibration mechanism suggests a requirement for symmetric AHV cells, the existence of which has previously been unexplained, and predicts that symmetric and asymmetric AHV cells should be distinctly different (in morphology, synaptic targets and/or methods of action on postsynaptic HD cells) due to their distinctly different functions.     

Phylogenetic profiles: a graphical method for detecting genetic recombinations in homologous sequences

Phylogenetic profiles constitute a novel way of graphically displaying the coherence of the sequence relationships over the entire length of a set of aligned homologous sequences. Using a sliding-window technique, this method determines the pairwise distances of all sequences in the windows and evaluates, for each sequence, the degree to which the patterns of distances in these regions agree. This method is suited for exploring data consistency as well as detecting recombinant sequences. A computer program implementing the algorithm has been developed, and examples with simulated and natural sequences are given to demonstrate the sensitivity and accuracy of the method for identifying recombinant sequences and their recombination junctions as well as detecting hot spots of recombinational activity.      

Demonstrating the utility of flexible sequence queries against indexed short reads with FlexTyper

Across the life sciences, processing next generation sequencing data commonly relies upon a computationally expensive process where reads are mapped onto a reference sequence. Prior to such processing, however, there is a vast amount of information that can be ascertained from the reads, potentially obviating the need for processing, or allowing optimized mapping approaches to be deployed. Here, we present a method termed FlexTyper which facilitates a “reverse mapping” approach in which high throughput sequence queries, in the form of k-mer searches, are run against indexed short-read datasets in order to extract useful information. This reverse mapping approach enables the rapid counting of target sequences of interest. We demonstrate FlexTyper’s utility for recovering depth of coverage, and accurate genotyping of SNP sites across the human genome. We show that genotyping unmapped reads can correctly inform a sample’s population, sex, and relatedness in a family setting. Detection of pathogen sequences within RNA-seq data was sensitive and accurate, performing comparably to existing methods, but with increased flexibility. We present two examples of ways in which this flexibility allows the analysis of genome features not well-represented in a linear reference. First, we analyze contigs from African genome sequencing studies, showing how they distribute across families from three distinct populations. Second, we show how gene-marking k-mers for the killer immune receptor locus allow allele detection in a region that is challenging for standard read mapping pipelines. The future adoption of the reverse mapping approach represented by FlexTyper will be enabled by more efficient methods for FM-index generation and biology-informed collections of reference queries. In the long-term, selection of population-specific references or weighting of edges in pan-population reference genome graphs will be possible using the FlexTyper approach. FlexTyper is available at https://github.com/wassermanlab/OpenFlexTyper.