Panoptes: web-based exploration of large scale genome variation data.

MOTIVATION: The size and complexity of modern large-scale genome variation studies demand novel approaches for exploring and sharing the data. In order to unlock the potential of these data for a broad audience of scientists with various areas of expertise, a unified exploration framework is required that is accessible, coherent and user-friendly. RESULTS: Panoptes is an open-source software framework for collaborative visual exploration of large-scale genome variation data and associated metadata in a web browser. It relies on technology choices that allow it to operate in near real-time on very large datasets. It can be used to browse rich, hybrid content in a coherent way, and offers interactive visual analytics approaches to assist the exploration. We illustrate its application using genome variation data of Anopheles gambiae, Plasmodium falciparum and Plasmodium vivax. AVAILABILITY AND IMPLEMENTATION: Freely available at https://github.com/cggh/panoptes, under the GNU Affero General Public License. CONTACT: paul.vauterin@gmail.com.

Preparation of stereoregular isotactic poly(mandelic acid) through organocatalytic ring-opening polymerization of a cyclic O-carboxyanhydride.

Poly(mandelic acid) (PMA) is an aryl analogue of poly(lactic acid) (PLA) and a biodegradable analogue of polystyrene. The preparation of stereoregular PMA was realized using a pyridine/mandelic acid adduct (Py⋅MA) as an organocatalyst for the ring-opening polymerization (ROP) of the cyclic O-carboxyanhydride (manOCA). Polymers with a narrow polydispersity index and excellent molecular-weight control were prepared at ambient temperature. These highly isotactic chiral polymers exhibit an enhancement of the glass-transition temperature (T(g)) of 15 °C compared to the racemic polymer, suggesting potential future application as high-performance commodity and biomedical materials.

Analysis-ready VCF at Biobank scale using Zarr.

Background: Variant Call Format (VCF) is the standard file format for interchanging genetic variation data and associated quality control metrics. The usual row-wise encoding of the VCF data model (either as text or packed binary) emphasises efficient retrieval of all data for a given variant, but accessing data on a field or sample basis is inefficient. Biobank scale datasets currently available consist of hundreds of thousands of whole genomes and hundreds of terabytes of compressed VCF. Row-wise data storage is fundamentally unsuitable and a more scalable approach is needed. Results: We present the VCF Zarr specification, an encoding of the VCF data model using Zarr which makes retrieving subsets of the data much more efficient. Zarr is a cloud-native format for storing multi-dimensional data, widely used in scientific computing. We show how this format is far more efficient than standard VCF based approaches, and competitive with specialised methods for storing genotype data in terms of compression ratios and calculation performance. We demonstrate the VCF Zarr format (and the vcf2zarr conversion utility) on a subset of the Genomics England aggV2 dataset comprising 78,195 samples and 59,880,903 variants, with a 5X reduction in storage and greater than 300X reduction in CPU usage in some representative benchmarks. Conclusions: Large row-encoded VCF files are a major bottleneck for current research, and storing and processing these files incurs a substantial cost. The VCF Zarr specification, building on widely-used, open-source technologies has the potential to greatly reduce these costs, and may enable a diverse ecosystem of next-generation tools for analysing genetic variation data directly from cloud-based object stores.

On the genes, genealogies, and geographies of Quebec.

Population genetic models only provide coarse representations of real-world ancestry. We used a pedigree compiled from 4 million parish records and genotype data from 2276 French and 20,451 French Canadian individuals to finely model and trace French Canadian ancestry through space and time. The loss of ancestral French population structure and the appearance of spatial and regional structure highlights a wide range of population expansion models. Geographic features shaped migrations, and we find enrichments for migration, genetic, and genealogical relatedness patterns within river networks across regions of Quebec. Finally, we provide a freely accessible simulated whole-genome sequence dataset with spatiotemporal metadata for 1,426,749 individuals reflecting intricate French Canadian population structure. Such realistic population-scale simulations provide opportunities to investigate population genetics at an unprecedented resolution.

A unified genealogy of modern and ancient genomes.

The sequencing of modern and ancient genomes from around the world has revolutionized our understanding of human history and evolution. However, the problem of how best to characterize ancestral relationships from the totality of human genomic variation remains unsolved. Here, we address this challenge with nonparametric methods that enable us to infer a unified genealogy of modern and ancient humans. This compact representation of multiple datasets explores the challenges of missing and erroneous data and uses ancient samples to constrain and date relationships. We demonstrate the power of the method to recover relationships between individuals and populations as well as to identify descendants of ancient samples. Finally, we introduce a simple nonparametric estimator of the geographical location of ancestors that recapitulates key events in human history.

Efficient ancestry and mutation simulation with msprime 1.0.

Stochastic simulation is a key tool in population genetics, since the models involved are often analytically intractable and simulation is usually the only way of obtaining ground-truth data to evaluate inferences. Because of this, a large number of specialized simulation programs have been developed, each filling a particular niche, but with largely overlapping functionality and a substantial duplication of effort. Here, we introduce msprime version 1.0, which efficiently implements ancestry and mutation simulations based on the succinct tree sequence data structure and the tskit library. We summarize msprime's many features, and show that its performance is excellent, often many times faster and more memory efficient than specialized alternatives. These high-performance features have been thoroughly tested and validated, and built using a collaborative, open source development model, which reduces duplication of effort and promotes software quality via community engagement.

Genomic analysis of local variation and recent evolution in Plasmodium vivax.

The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.

Group 4 initiators for the stereoselective ROP of rac-ß-butyrolactone and its copolymerization with rac-lactide.

In this paper we demonstrate the utility of Group 4 metals for the well-controlled and stereoselective (syndiotactic) ring opening polymerization (ROP) of rac-ß-butyrolactone (BBL) and their ability to form copolymers.