Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Genomics promises comprehensive surveying of genomes and metagenomes, but rapidly changing technologies and expanding data volumes make evaluation of completeness a challenging task. Technical sequencing quality metrics can be complemented by quantifying completeness of genomic data sets in terms of the expected gene content of Benchmarking Universal Single-Copy Orthologs (BUSCO, http://busco.ezlab.org). The latest software release implements a complete refactoring of the code to make it more flexible and extendable to facilitate high-throughput assessments. The original six lineage assessment data sets have been updated with improved species sampling, 34 new subsets have been built for vertebrates, arthropods, fungi, and prokaryotes that greatly enhance resolution, and data sets are now also available for nematodes, protists, and plants. Here, we present BUSCO v3 with example analyses that highlight the wide-ranging utility of BUSCO assessments, which extend beyond quality control of genomics data sets to applications in comparative genomics analyses, gene predictor training, metagenomics, and phylogenomics.

https://serval.unil.ch/resource/serval:BIB_2A4C7F8DA305.P001/REF.pdf

BUSCO Applications from Quality Assessments to Gene Prediction and Phylogenomics.

What is ecological speciation

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

A High-Resolution Map of Human Evolutionary Constraint Using 29 Mammals

To instill greater confidence in computations outsourced to the cloud, clients should be able to verify the correctness of the results returned. To this end, we introduce Pinocchio, a built system for efficiently verifying general computations while relying only on cryptographic assumptions. With Pinocchio, the client creates a public evaluation key to describe her computation; this setup is proportional to evaluating the computation once. The worker then evaluates the computation on a particular input and uses the evaluation key to produce a proof of correctness. The proof is only 288 bytes, regardless of the computation performed or the size of the inputs and outputs. Anyone can use a public verification key to check the proof. Crucially, our evaluation on seven applications demonstrates that Pinocchio is efficient in practice too. Pinocchio's verification time is typically 10ms: 5-7 orders of magnitude less than previous work; indeed Pinocchio is the first general-purpose system to demonstrate verification cheaper than native execution (for some apps). Pinocchio also reduces the worker's proof effort by an additional 19-60x. As an additional feature, Pinocchio generalizes to zero-knowledge proofs at a negligible cost over the base protocol. Finally, to aid development, Pinocchio provides an end-to-end toolchain that compiles a subset of C into programs that implement the verifiable computation protocol.

/pdf/pinocchio-nearly-practical-verifiable-computation-4z07ssgjg5.pdf

Pinocchio: Nearly Practical Verifiable Computation

Introgressive hybridization is now recognized as a widespread phenomenon, but its role in evolution remains contested. Here, we use newly available reference genome assemblies to investigate phylogenetic relationships and introgression in a medically important group of Afrotropical mosquito sibling species. We have identified the correct species branching order to resolve a contentious phylogeny and show that lineages leading to the principal vectors of human malaria were among the first to split. Pervasive autosomal introgression between these malaria vectors means that only a small fraction of the genome, mainly on the X chromosome, has not crossed species boundaries. Our results suggest that traits enhancing vectorial capacity may be gained through interspecific gene flow, including between nonsister species.

https://science.sciencemag.org/content/sci/347/6217/1258524.full.pdf

Extensive introgression in a malaria vector species complex revealed by phylogenomics

Secure computation on private data has been an active area of research for many years and has received a renewed interest with the emergence of cloud computing. In recent years, substantial progress has been made with respect to the efficiency of the available techniques and several implementations have appeared. The available tools, however, lacked a convenient mechanism for implementing a general-purpose}program in a secure computation framework suitable for execution in not fully trusted environments. This work fulfills this gap and describes a system, called PICCO, for converting a program written in an extension of C into its distributed secure implementation and running it in a distributed environment. The C extension preserves all current features of the programming language and allows variables to be marked as private and be used in general-purpose computation. Secure distributed implementation of compiled programs is based on linear secret sharing, achieving efficiency and information-theoretical security. Our experiments also indicate that many programs can be evaluated very efficiently on private data using PICCO.

PICCO: a general-purpose compiler for private distributed computation

This work treats the problem of designing data-oblivious algorithms for classical and widely used graph problems. A data-oblivious algorithm is defined as having the same sequence of operations regardless of the input data and data-independent memory accesses. Such algorithms are suitable for secure processing in outsourced and similar environments, which serves as the main motivation for this work. We provide data-oblivious algorithms for breadth-first search, single-source single-destination shortest path, minimum spanning tree, and maximum flow, the asymptotic complexities of which are optimal, or close to optimal, for dense graphs.

Data-oblivious graph algorithms for secure computation and outsourcing

Secure computation undeniably received a lot of attention in the recent years, with the shift toward cloud computing offering a new incentive for secure computation and outsourcing. Surprisingly little attention, however, has been paid to computation with non-integer data types. To narrow this gap, in this work we develop efficient solutions for computation with real numbers in floating point representation, as well as more complex operations such as square root, logarithm, and exponentiation. Our techniques are information-theoretically secure, do not use expensive cryptographic techniques, and can be applied to a variety of settings. Our experimental results also show that the techniques exhibit rather fast performance and in some cases outperform operations on integers.

Secure Computation on Floating Point Numbers.

Synonymous rare codons are considered to be sub-optimal for gene expression because they are translated more slowly than common codons. Yet surprisingly, many protein coding sequences include large clusters of synonymous rare codons. Rare codons at the 5' terminus of coding sequences have been shown to increase translational efficiency. Although a general functional role for synonymous rare codons farther within coding sequences has not yet been established, several recent reports have identified rare-to-common synonymous codon substitutions that impair folding of the encoded protein. Here we test the hypothesis that although the usage frequencies of synonymous codons change from organism to organism, codon rarity will be conserved at specific positions in a set of homologous coding sequences, for example to tune translation rate without altering a protein sequence. Such conservation of rarity-rather than specific codon identity-could coordinate co-translational folding of the encoded protein. We demonstrate that many rare codon cluster positions are indeed conserved within homologous coding sequences across diverse eukaryotic, bacterial, and archaeal species, suggesting they result from positive selection and have a functional role. Most conserved rare codon clusters occur within rather than between conserved protein domains, challenging the view that their primary function is to facilitate co-translational folding after synthesis of an autonomous structural unit. Instead, many conserved rare codon clusters separate smaller protein structural motifs within structural domains. These smaller motifs typically fold faster than an entire domain, on a time scale more consistent with translation rate modulation by synonymous codon usage. While proteins with conserved rare codon clusters are structurally and functionally diverse, they are enriched in functions associated with organism growth and development, suggesting an important role for synonymous codon usage in organism physiology. The identification of conserved rare codon clusters advances our understanding of distinct, functional roles for otherwise synonymous codons and enables experimental testing of the impact of synonymous codon usage on the production of functional proteins.

/pdf/widespread-position-specific-conservation-of-synonymous-rare-51gnig6so4.pdf

Aaron Steele

Papers

Extensive introgression in a malaria vector species complex revealed by phylogenomics

PICCO: a general-purpose compiler for private distributed computation

Data-oblivious graph algorithms for secure computation and outsourcing

Secure Computation on Floating Point Numbers.

Widespread position-specific conservation of synonymous rare codons within coding sequences