The ability of single genes vs full genomes to resolve time and space in outbreak analysis, bioRxiv, 2019-03-24

AbstractInexpensive pathogen genome sequencing has had a transformative effect on the field of phylodynamics, where ever increasing volumes of data have promised real-time insight into outbreaks of infectious disease. As well as the sheer volume of pathogen isolates being sequenced, the sequencing of whole pathogen genomes, rather than select loci, has allowed phylogenetic analyses to be carried out at finer time scales, often approaching serial intervals for infections caused by rapidly evolving RNA viruses. Despite its utility, whole genome sequencing of pathogens has not been adopted universally and targeted sequencing of loci is common in some pathogen-specific fields. In this study we aim to highlight the utility of sequencing whole genomes of pathogens by re-analysing a well-characterised collection of Ebola virus sequences in the form of complete viral genomes (~19kb long) or the rapidly evolving glycoprotein (GP, ~2kb long) gene. We quantify changes in phylogenetic, temporal, and spatial inference resolution as a result of this reduction in data and compare these to theoretical expectations. We propose a simple intuitive metric for quantifying temporal resolution, i.e. the time scale over which sequence data might be informative of various processes as a quick back-of-the-envelope calculation of statistical power available to molecular clock analyses.

biorxiv epidemiology 0-100-users 2019

An image-computable model for the stimulus selectivity of gamma oscillations, bioRxiv, 2019-03-22

AbstractGamma oscillations in visual cortex have been hypothesized to be critical for perception, cognition, and information transfer. However, observations of these oscillations in visual cortex vary widely; some studies report little to no stimulus-induced narrowband gamma oscillations, others report oscillations for only some stimuli, and yet others report large oscillations for most stimuli. To reconcile these findings and better understand this signal, we developed a model that predicts gamma responses for arbitrary images and validated this model on electrocorticography (ECoG) data from human visual cortex. The model computes variance across the outputs of spatially pooled orientation channels, and accurately predicts gamma amplitude across 86 images. Gamma responses were large for a small subset of stimuli, differing dramatically from fMRI and ECoG broadband (non-oscillatory) responses. We suggest that gamma oscillations in visual cortex serve as a biomarker of gain control rather than being a fundamental mechanism for communicating visual information.

biorxiv neuroscience 0-100-users 2019

Mitigating Pandemic Risk with Influenza A Virus Field Surveillance at a Swine-Human Interface, bioRxiv, 2019-03-22

Working overnight at a large swine exhibition, we identified an influenza A virus (IAV) outbreak in swine, nanopore-sequenced 13 IAV genomes from samples collected, and in real-time, determined that these viruses posed a novel risk to humans due to genetic mismatches between the viruses and current pre-pandemic candidate vaccine viruses (CVV). We developed and used a portable IAV sequencing and analysis platform called Mia (Mobile Influenza Analysis) to complete and characterize full-length consensus genomes approximately 18 hours after unpacking the mobile lab. Swine are important animal IAV reservoirs that have given rise to pandemic viruses via zoonotic transmission. Genomic analyses of IAV in swine are critical to understanding pandemic risk of viruses in this reservoir, and characterization of viruses circulating in exhibition swine enables rapid comparison to current seasonal influenza vaccines and CVVs. The Mia system rapidly identified three genetically distinct swine IAV lineages from three subtypes A(H1N1), A(H3N2) and A(H1N2). Additional analysis of the HA protein sequences of the A(H1N2) viruses identified >30 amino acid differences between the HA1 portion of the hemagglutinin of these viruses and the most closely related pre-2009 CVV. All virus sequences were emailed to colleagues at CDC who initiated development of a synthetically derived CVV designed to provide an optimal antigenic match with the viruses detected in the exhibition. In subsequent months, this virus caused 13 infections in humans, and was the dominant variant virus in the US detected in 2018. Had this virus caused a severe outbreak or pandemic, our proactive surveillance efforts and CVV derivation would have provided an approximate 8 week time advantage for vaccine manufacturing. This is the first report of the use of field-derived nanopore sequencing data to initiate a real-time, actionable public health countermeasure.

biorxiv microbiology 0-100-users 2019

Structural color in Junonia butterflies evolves by tuning scale lamina thickness, bioRxiv, 2019-03-22

AbstractStructural color is a pervasive natural phenomenon, caused by photonic nanostructures that refract light. Diverse organisms employ structural color to mediate ecological interactions and create specific optical effects such as iridescence. Despite its importance for living systems, the developmental, genetic, and evolutionary processes that generate structural color largely remain mysterious. Here, we focus on simple photonic structures, thin film reflectors, in the lower lamina of Junonia butterfly scales. We present multiple lines of evidence that the thickness of the lamina quantitatively controls lamina color, which is an important determinant of overall wing color, even when pigments are also present. First, in a lineage of buckeye butterflies artificially selected for blue wing color for 12 generations, a thicker lamina resulted in a color shift from brown to blue. A similar lamina thickness increase explains the appearance of blue scales in butterflies with mutations in the optix wing patterning gene. Finally, lamina thickness variation underlies the color diversity that distinguishes seasonal variants, sexes, and species throughout the genus Junonia. Thus, quantitatively tuning a single dimension of the existing scale architecture allows butterflies to evolve a broad spectrum of hues over both microevolutionary and macroevolutionary time frames. Because the lower lamina is an intrinsic component of typical butterfly scales, our findings imply that lamina structural color influences wing color in most butterflies.Significance StatementStructural colors, which result from photonic nanostructures that refract light and can create iridescence, are an important tool for many organisms. We use thin films, which are morphologically simple nanostructures that generate structural color in the lower lamina of butterfly scales, to dissect how photonic structures evolve. By combining interspecies comparisons with two different experimental approaches—artificial selection on wing color, and genetically engineered mutation of the optix wing patterning gene—we demonstrate that lamina thickness controls the wavelength (hue) of the structural color. These lamina structural colors are ubiquitous in the genus Junonia, and determine wing color along with pigments. Our results suggest that lamina structural colors probably exist in most butterflies, and that tuning lamina thickness facilitates wing color evolution.

biorxiv evolutionary-biology 0-100-users 2019

The Arrival of Steppe and Iranian Related Ancestry in the Islands of the Western Mediterranean, bioRxiv, 2019-03-21

A series of studies have documented how Steppe pastoralist-related ancestry reached central Europe by at least 2500 BCE, while Iranian farmer-related ancestry was present in Aegean Europe by at least 1900 BCE. However, the spread of these ancestries into the western Mediterranean where they have contributed to many populations living today remains poorly understood. We generated genome-wide ancient DNA from the Balearic Islands, Sicily, and Sardinia, increasing the number of individuals with reported data from these islands from 3 to 52. We obtained data from the oldest skeleton excavated from the Balearic islands (dating to ∼2400 BCE), and show that this individual had substantial Steppe pastoralist-derived ancestry; however, later Balearic individuals had less Steppe heritage reflecting geographic heterogeneity or immigration from groups with more European first farmer-related ancestry. In Sicily, Steppe pastoralist ancestry arrived by ∼2200 BCE and likely came at least in part from Spain as it was associated with Iberian-specific Y chromosomes. In Sicily, Iranian-related ancestry also arrived by the Middle Bronze Age, thus revealing that this ancestry type, which was ubiquitous in the Aegean by this time, also spread further west prior to the classical period of Greek expansion. In Sardinia, we find no evidence of either eastern ancestry type in the Nuragic Bronze Age, but show that Iranian-related ancestry arrived by at least ∼300 BCE and Steppe ancestry arrived by ∼300 CE, joined at that time or later by North African ancestry. These results falsify the view that the people of Sardinia are isolated descendants of Europe’s first farmers. Instead, our results show that the island’s admixture history since the Bronze Age is as complex as that in many other parts of Europe.

biorxiv genomics 0-100-users 2019

Direct visualization of single nuclear pore complex proteins using genetically-encoded probes for DNA-PAINT, bioRxiv, 2019-03-20

The Nuclear Pore Complex (NPC) is one of the largest and most complex protein assemblies in the cell and – among other functions – serves as the gatekeeper of nucleocytoplasmic transport. Unraveling its molecular architecture and functioning has been an active research topic for decades with recent cryogenic electron microscopy and superresolution studies advancing our understanding of the NPC's complex architecture. However, the specific and direct visualization of single copies of NPC proteins and thus the ability to observe single-molecule heterogeneities of these complex structures is thus far elusive. Here, we combine genetically-encoded self-labeling enzymes such as SNAP-tag and HaloTag with DNA-PAINT microscopy. We employ the high localization precision in DNA-PAINT and molecular contrast of these protein tags to optically resolve single copies of nucleoporins in the human Y-complex in three dimensions with a precision of ~3 nm. This technological advancement now enables structural studies of multicomponent complexes on the level of single proteins in cells using optical fluorescence microscopy.

biorxiv cell-biology 0-100-users 2019