We introduce Giraffe, a pangenome short-read mapper that can efficiently map to a collection of haplotypes threaded through a sequence graph. Giraffe maps sequencing reads to thousands of human ...genomes at a speed comparable to that of standard methods mapping to a single reference genome. The increased mapping accuracy enables downstream improvements in genome-wide genotyping pipelines for both small variants and larger structural variants. We used Giraffe to genotype 167,000 structural variants, discovered in long-read studies, in 5202 diverse human genomes that were sequenced using short reads. We conclude that pangenomics facilitates a more comprehensive characterization of variation and, as a result, has the potential to improve many genomic analyses.
A challenge that conservation practitioners face is manipulating behavior of nuisance species. The turkey vulture (Cathartes aura) can cause substantial damage to aircraft if struck. The goal of this ...study was to assess vulture responses to unmanned aircraft systems (UAS) for use as a possible dispersal tool. Our treatments included three platforms (fixed-wing, multirotor, and a predator-like ornithopter powered by flapping flight) and two approach types (30 m overhead or targeted towards a vulture) in an operational context. We evaluated perceived risk as probability of reaction, reaction time, flight-initiation distance (FID), vulture remaining index, and latency to return. Vultures escaped sooner in response to the fixed-wing; however, fewer remained after multirotor treatments. Targeted approaches were perceived as riskier than overhead. Vulture perceived risk was enhanced by flying the multirotor in a targeted approach. We found no effect of our treatments on FID or latency to return. Latency was negatively correlated with UAS speed, perhaps because slower UAS spent more time over the area. Greatest visual saliency followed as: ornithopter, fixed-wing, and multirotor. Despite its appearance, the ornithopter was not effective at dispersing vultures. Because effectiveness varied, multirotor/fixed-wing UAS use should be informed by management goals (immediate dispersal versus latency).
The avoidance of motorized vehicles is a common challenge for birds in the modern world. Birds appear to rely on antipredator behaviors to avoid vehicles, but modern vehicles (automobiles and ...aircraft) are faster than natural predators. Thus, birds may be relatively ill-equipped, in terms of sensory capabilities and behaviors, to avoid vehicles. We examined the idea that birds may be unable to accurately assess particularly high speeds of approaching vehicles, which could contribute to miscalculations in avoidance behaviors and ultimately cause collisions. We baited turkey vultures (Cathartes aura) to roads with animal carcasses and measured flight initiation distance and effective time-to-collision in response to a truck driving directly towards vultures from a starting distance of 1.13 km and at one of three speeds: 30, 60, or 90 kph (no vultures were struck). Flight initiation distance of vultures increased by a factor of 1.85 as speed increased from 30 to 90 kph. However, for 90-kph approaches there was no clear trend in flight initiation distance across replicates: birds appeared equally likely to initiate escape behavior at 40 m as at 220 m. Time-to-collision decreased by a factor of 0.62 with approach speeds from 30 to 90 kph. Also, at 90 kph, four vehicle approaches (17%) resulted in near collisions with vultures (time-to-collision ≤1.7 s), compared to none during 60 kph approaches and one during 30 kph approaches (4%). Our findings suggest that antipredator behaviors in turkey vultures, particularly stimulus processing and response, might not be well tuned to vehicles approaching at speeds ≥90 kph. The possible inability of turkey vultures to react appropriately to high-speed vehicles could be common among birds, and might represent an important determinant of bird-vehicle collisions.
The fundamental causes of animal-vehicle collisions are unclear, particularly at the level of animal detection of approaching vehicles and decision-making. Deer-vehicle collisions (DVCs) are ...especially costly in terms of animal mortality, property damage, and safety. Over one year, we exposed free-ranging white-tailed deer (Odocoileus virginianus) to vehicle approach under low ambient light conditions, from varying start distances, and vehicle speeds from 20 km/h to approximately 90 km/h. We modeled flight response by deer to an approaching vehicle and tested four hypotheses: 1) flight-initiation distance (FID) would correlate positively with start distance (indicating a spatial margin of safety); 2) deer would react to vehicle speed using a temporal margin of safety; 3) individuals reacting at greater FIDs would be more likely to cross the path of the vehicle; and 4) crossings would correlate positively with start distance, approach speed, and distance to concealing/refuge cover. We examined deer responses by quantiles. Median FID was 40% of start distance, irrespective of start distance or approach speed. Converting FID to time-to-collision (TTC), median TTC was 4.6 s, but uncorrelated with start distance or approach speed. The likelihood of deer crossing in front of the vehicle was not associated with greater FIDs or other explanatory variables. Because deer flight response to vehicle approach was highly variable, DVCs should be more likely with increasing vehicle speeds because of lower TTCs for a given distance. For road sections characterized by frequent DVCs, we recommend estimating TTC relative to vehicle speed and candidate line-of-sight distances adjusted downward by (1-P), where P represents our findings for the proportion of start distance by which >75% of deer had initiated flight. Where road design or conservation goals limit effectiveness of line-of-sight maintenance, we suggest incorporation of roadway obstacles that force drivers to slow vehicles, in addition to posting advisory speed limits.
Animal–vehicle collisions cause many millions of animal deaths each year worldwide and present a substantial safety risk to people. In the United States and Canada, deer (Odocoileus spp.) are ...involved in most animal–vehicle collisions associated with human injuries. We evaluated a vehicle‐based collision mitigation method designed to decrease the likelihood of deer–vehicle collisions during low‐light conditions, when most collisions occur. Specifically, we investigated whether the use of a rear‐facing light, providing more complete frontal vehicle illumination than standard headlights alone, enhanced vehicle avoidance behaviors of white‐tailed deer (O. virginianus). We quantified flight initiation distance (FID), the likelihood of a dangerous deer–vehicle interaction (FID ≤ 50 m), and road‐crossing behavior of deer in response to an oncoming vehicle using only standard high‐beam headlights and the same vehicle using headlights plus an LED light bar illuminating the frontal surface of the vehicle. We predicted that frontal vehicle illumination would enhance perceived risk of deer approached by the vehicle and lead to more effective avoidance responses. We conducted 62 vehicle approaches (31 per lighting treatment) toward free‐ranging deer over ~14 months. Although FID did not differ across treatments, the likelihood of a dangerous deer–vehicle interaction decreased from 35% of vehicle approaches using only headlights to 10% of vehicle approaches using the light bar. The reduction in dangerous interactions appeared to be driven by fewer instances of immobility (freezing) behavior by deer in response to the illuminated vehicle (n = 1) compared with approaches using only headlights (n = 10). Because more deer moved in response to the illuminated vehicle, road‐crossing behavior likewise increased when the light bar was on, although these road crossings primarily occurred at FIDs > 50 m and thus did not increase collision risk. Road‐crossing behavior was influenced heavily by proximity to concealing cover; deer only crossed when the nearest cover was located on the opposite side of the road. We contend that frontal vehicle illumination via rear‐facing lighting has potential to greatly reduce vehicle collisions with deer and other species. Future work should explore fine‐tuning the method with regard to the visual capabilities of target species.
Type 1 diabetes is an autoimmune disease characterised by selective destruction of pancreatic beta cells by the immune system. The transcription factor nuclear factor-kappa B (NF-κB) regulates innate ...and adaptive immune responses. Using gene targeting and in vitro analysis of pancreatic islets and immune cells, NF-κB activation has been implicated in type 1 diabetes development. Here we use a non-obese diabetic (NOD) mouse model that expresses a luciferase reporter of transcriptionally active NF-κB to determine its activation in vivo during development of diabetes. Increased luciferase activity was readily detected upon treatment with Toll-like receptor ligands in vitro and in vivo, indicating activation of NF-κB. However, activated NF-κB was detectable at low levels above background in unmanipulated NOD mice, but did not vary with age, despite the progression of inflammatory infiltration in islets over time. NF-κB was highly activated in an accelerated model of type 1 diabetes that requires CD4
T cells and inflammatory macrophages. These data shed light on the nature of the inflammatory response in the development of type 1 diabetes.
Animal–vehicle collisions cause high levels of vertebrate mortality worldwide, and what goes wrong when animals fail to escape and ultimately collide with vehicles is not well understood. We ...investigated alert and escape behaviours of captive brown-headed cowbirds (Molothrus ater) in response to virtual vehicle approaches of different sizes and at speeds ranging from 60 to 360 km h−1. Alert and flight initiation distances remained similar across vehicle speeds, and accordingly, alert and flight initiation times decreased at higher vehicle speeds. Thus, avoidance behaviours in cowbirds appeared to be based on distance rather than time available for escape, particularly at 60–150 km h−1; however, at higher speeds (more than or equal to 180 km h−1) no trend in response behaviour was discernible. As vehicle speed increased, cowbirds did not have enough time to assess the approaching vehicle, and cowbirds generally did not initiate flight with enough time to avoid collision when vehicle speed exceeded 120 km h−1. Although potentially effective for evading predators, the decision-making process used by cowbirds in our study appears maladaptive in the context of avoiding fast-moving vehicles. Our methodological approach and findings provide a framework to assess how novel management strategies could affect escape rules, and the sensory and cognitive abilities animals use to avoid vehicle collisions.
Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, ...we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.
To identify regulatory variants with plasticity in effect size, we performed interaction molecular quantitative trait loci (iQTL) mapping with cell-type abundance, age, sex, and smoking as the environmental factors. Our results highlight the usefulness of iQTLs for gaining insights into the context specificity of regulatory effects.
The Human Proteome Organization (HUPO) recently completed the first large-scale collaborative study to characterize the human serum and plasma proteomes. The study was carried out in different ...locations and used diverse methods and instruments to compare and integrate tandem mass spectrometry (MS/MS) data on aliquots of pooled serum and plasma from healthy subjects. Liquid chromatography (LC)-MS/MS data sets from 18 laboratories were matched to the International Protein Index database, and an initial integration exercise resulted in 9,504 proteins identified with one or more peptides, and 3,020 proteins identified with two or more peptides. This article uses a rigorous statistical approach to take into account the length of coding regions in genes, and multiple hypothesis-testing techniques. On this basis, we now present a reduced set of 889 proteins identified with a confidence level of at least 95%. We also discuss the importance of such an integrated analysis in providing an accurate representation of a proteome as well as the value such data sets contain for the high-confidence identification of protein matches to novel exons, some of which may be localized in alternatively spliced forms of known plasma proteins and some in previously nonannotated gene sequences.
Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 ...individuals in the 1000 Genomes Project. Here, we present TOP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. TOP-LD provides a significant upgrade compared to current LD tools, as the TOPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we analyzed. For example, TOP-LD encompasses LD information for 150.3, 62.2, and 36.7 million variants for European, African, and East Asian ancestral samples, respectively, offering 2.6- to 9.1-fold increase in variant coverage compared to HaploReg 4.0 or LDlink. In addition, TOP-LD includes tens of thousands of structural variants (SVs). We demonstrate the value of TOP-LD in fine-mapping at the GGT1 locus associated with gamma glutamyltransferase in the African ancestry participants in UK Biobank. Beyond fine-mapping, TOP-LD can facilitate a wide range of applications that are based on summary statistics and estimates of LD. TOP-LD is freely available online.
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