Biology subjects

Kelly, J.

Publications and source records attributed to Kelly, J..

34 records · Page 2Linked to original sources

bioRxiv2024

Detection of ATTR aggregates in plasma of polyneuropathic ATTR-V30M amyloidosis patients

ATTR amyloidosis is caused by the deposition of transthyretin amyloid fibrils in tissues often leading to organ failure and death. The clinical spectrum of this disease is highly diverse and dependent on many factors including the presence or absence of mutations within the transthyretin protein and/or an individuals ancestry. The phenotypic variability of ATTR amyloidosis makes it difficult to diagnose, delaying treatment and worsening patient prognosis. Our lab has recently developed a peptide probe that detects transthyretin aggregates in plasma of ATTR amyloidosis patients with cardiomyopathy but has not been tested in plasma from polyneuropathic patients. Here we evaluate our probe in a cohort of Portuguese patients carrying the ATTR-V30M mutation and having no cardiac phenotype. We found that we could indeed detect aggregates in their plasma, and there appeared to be no relationship between the presence of aggregates and patient age or gender. Our work has broad implications on the pathobiology of ATTR amyloidosis and contribute to the validation of our probe as a novel detection tool for this disease.

biochemistry↗

bioRxiv2024

AutoXAI4Omics: an Automated Explainable AI tool for Omics and tabular data

Machine learning (ML) methods have the potential of detailed insights of complex biological systems and today are increasingly used to analyse omics data for tasks such as the discovery of novel biomarkers and phenotype prediction. It can be extremely beneficial and powerful for scientists, domain experts, to easily run sophisticated, robust, and interpretable ML pipelines without the need for an in depth understanding of the code needed to train, tune, optimise ML algorithms. They can then focus on the biological interpretation and validation of the results and insights generated by ML models. Here, we present an entirely automated open-source explainable AI tool, AutoXAI4Omics, that performs classification and regression tasks from omics and tabular numerical data. AutoXAI4Omics accelerates scientific discovery by automating processes and decisions made by AI experts, e.g., selection of the best feature set, hyper-tuning of different ML algorithms and selection of the best ML model for a specific task and dataset. Prior to ML analysis AutoXAI4Omics incorporates feature filtering options that are tailored to specific omic data types. Moreover, the insights into the predictions that are provided by the tool through explainability analysis highlight associations between omic feature values and the targets under investigation e.g., predicted phenotypes, facilitating the discovery of actionable insights. AutoXAI4Omics is at: https://github.com/IBM/AutoXAI4Omics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=188 HEIGHT=200 SRC="FIGDIR/small/586460v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@366327org.highwire.dtl.DTLVardef@a7b559org.highwire.dtl.DTLVardef@7319aforg.highwire.dtl.DTLVardef@9b5030_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2024

Tumor cell-based liquid biopsy using high-throughput microfluidic enrichment of entire leukapheresis product

Circulating Tumor Cells (CTCs), interrogated by sampling blood from patients with cancer, contain multiple analytes, including intact RNA, high molecular weight DNA, proteins, and metabolic markers. However, the clinical utility of tumor cell-based liquid biopsy has been limited since CTCs are very rare, and current technologies cannot process the blood volumes required to isolate a sufficient number of tumor cells for in-depth assays. We previously described a high-throughput microfluidic prototype utilizing high-flow channels and amplification of cell sorting forces through magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.83 liters from patients with metastatic cancer, with a median of 2,799 CTCs purified per patient. Isolation of many CTCs from individual patients enables characterization of their morphological and molecular heterogeneity, including cell and nuclear size and RNA expression. It also allows robust detection of gene copy number variation, a definitive cancer marker with potential diagnostic applications. High-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies.

bioengineering↗

bioRxiv2023

PET imaging of fibroblast activation protein alpha (FAP) detects incipient cardiotoxicity due to anthracycline chemotherapy

BackgroundAnthracycline chemotherapy is associated with a risk of cardiotoxicity leading to heart disease, particularly in pediatric cancer patients. Gold standard methods of detecting cardiotoxicity are insufficiently sensitive to early damage and specific pathophysiologies driving disease. Positron emission tomography (PET) couples anatomical resolution with biochemical mechanistic selectivity and potentially addresses the current diagnostic limitations in cardio-oncology. We aimed to validate PET imaging biomarkers targeting fibroblast activation protein alpha (FAP), Translocator protein (TSPO), and norepinephrine receptor (NET) for detection of incipient anthracycline-induced cardiotoxicity. MethodsCardiotoxicity was established in male C57BL/6J mice by a cumulative dose of 24 mg/kg doxorubicin (DOX) over 2 weeks. DOX mice and their age-matched controls were imaged with echocardiography and PET, using [68Ga]Ga-FAPI-04, [18F]DPA-714, and [18F]MFBG, over 12 weeks. Fractional shortening (FS) was determined from the echocardiograms, and cardiac uptake of the radioligands was quantified from the PET images. Heart sections were collected and used for the analysis of bulk RNA-seq, RT-qPCR, Western blot, in situ hybridization (ISH), and histopathological analysis. ResultsDOX mice exhibited cardiotoxicity and cardiac atrophy. Cardiac [68Ga]Ga-FAPI-04 PET signal was significantly higher in DOX mice from 2 weeks through the study endpoint. By contrast, no cardiac dysfunction was evident by echocardiography until 10 weeks, at which point FS was significantly reduced in DOX mice. There were no differences in [18F]DPA-714 and [18F]MFBG signals. Transcription and translation of FAP, but not TSPO or NET, was detected in cardiomyocytes and were elevated in the DOX hearts, in agreement with the PET data. Genes related to cell adhesion and extracellular remodeling were significantly upregulated in the DOX mice relative to controls. ConclusionsFAP is a sensitive and selective imaging biomarker for incipient cardiotoxicity and FAPI PET is a promising non-invasive imaging tool for identifying patients at risk of cardiotoxicity during or after anthracycline chemotherapy. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/556130v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@1d9e717org.highwire.dtl.DTLVardef@d2bde8org.highwire.dtl.DTLVardef@1b1f2c5org.highwire.dtl.DTLVardef@1b99bc6_HPS_FORMAT_FIGEXP M_FIG C_FIG NOVELTY AND SIGNIFICANCEO_ST_ABSWhat is Known?C_ST_ABSO_LIAnthracycline chemotherapy results in cardiotoxicity for a sizeable population of treated patients. Cardiotoxocity manifests as cardiac dysfunction, and may result in long-term cardiac disease and heart failure, particularly in survivors of pediatric cancer. C_LIO_LICardiotoxicity is typically defined in terms of left ventricular ejection fraction (LVEF) deficits, as measured by echocardiography. However, this metric is often poorly sensitive to early disease and agnostic to underlying pathophysiology. C_LIO_LIEarly treatment of cardiotoxicity improves recovery and long-term survival, emphasizing the need for accurate diagnostics in incipient disease. C_LI What New Information Does This Article Contain?O_LI[68Ga]Ga-FAPI-04 accumulates in the hearts of mice experiencing doxorubicin-induced cardiotoxicity as a function of fibroblast activation protein alpha (FAP) expression and activity. By contrast, cardiac uptake of radioligands targeting the translocator protein 18-kDa (TSPO) and the norepinephrine transporter (NET) do not differ between DOX animals and controls. C_LIO_LIPositron emission tomography (PET) imaging following administration of [68Ga]Ga-FAPI-04 detects abnormal cardiac remodeling significantly earlier than LVEF decrease is observed, indicating that it may be more sensitive to incipient disease. C_LI Our study identifies fibroblast activation protein alpha (FAP) as a promising diagnostic imaging biomarker in anthracycline-induced cardiotoxicity. We show that cardiac PET signal increases immediately after doxorubicin treatment, and the signal increase is sustained for at least 10 weeks. In addition, we demonstrate that FAP inhibitor (FAPI) PET correlates with expression of FAP protein and gene. Thus, we provide mechanistic insight into potentially-treatable pathophysiologies driving cardiac atrophy and toxicity, and have identified a translational PET tracer that can image the activation of these processes at an early stage.

cancer biology↗

bioRxiv2023

PROTEIN-O-MANNOSYLATION BY NON-SEC/TAT SECRETION TRANSLOCONS IN ACTINOBACTERIA

Protein-O-mannosylation (POM) is a form of O-glycosylation that is ubiquitous throughout all domains of life and has been extensively characterized in eukaryotic systems. However, in prokaryotes this process has only been investigated in terms of pathogenicity (in Mycobacterium tuberculosis) even though there are many non-pathogenic bacteria that are known to regularly carry out POM. To date, there is no consensus on what benefit POM imparts to the non-pathogenic bacteria that can perform it. Though the generation of a POM deficient mutant of Corynebacterium glutamicum - a widely utilized and known mannosylating actinobacteria - this work shows that even closely related actinobacterial GT-39s (the enzymes responsible for the initiation of POM) can potentially have different activities and substrate specificities for targets of POM. Moreover, presented here is evidence that POM does not only occur in a SEC-dependent manner; POM also occurs with TAT and non-SEC secreted substrates in a specific and likely tightly regulated manner. Together these results highlight the need for further biochemical characterization of POM in these and other bacterial species to help elucidate the true nature of its biological functions. ImportanceBoth the mechanism and overall cellular function of protein-O-mannosylation, a ubiquitous subset of O-glycosylation, is poorly understood in bacterial systems. In Mycobacterium tuberculosis and other pathogenic actinobacteria, numerous secreted virulence factors were identified as mannoproteins, with protein-O-mannosylation deficient mutants displaying a less virulent phenotype due to these proteins lacking the modification. However, these findings do not offer any explanations as to why non-pathogenic strains of actinobacteria also perform this modification as in these organisms it is seemingly dispensable. Corynebacterium glutamicum is a widely utilized, industrially relevant actinobacteria that also performs protein-O-mannosylation. This manuscript describes the utilization of C. glutamicum as a Gram-positive recombinant host for the in vivo study of actinobacterial protein-O-mannosylation and demonstrates the distinct lack of first-hand biochemical data of the process in prokaryotes.

microbiology↗

bioRxiv2022

Using spatio-temporal information in weather radar data to detect and track communal bird roosts

O_LIThe exodus of swallows from communal nighttime roosts is often visible as an expanding ring-shaped pattern in weather radar data. The WSR-88D network operated by the National Weather Service archives more than 25 years of data across 143 stations in the contiguous US. However, access to information about the roosting behavior of swallows is limited by the cost of manual annotation of these scans. C_LIO_LIWe develop an AI system to detect and track swallow roosts in weather radar data. Our model is based on the Faster R-CNN architecture and is customized to incorporate multiple spatial and temporal channels in volumetric radar scans using novel adaptor layers. We systematically study the impact of network architecture and input representation for this task. We incorporate our detection outputs into an AI-assisted system with an interface for human screening to collect research-grade data about roosting behavior. We deploy the system to collect information from 12 radar stations in the Great Lakes region of the US spanning 21 years. C_LIO_LIThe addition of temporal information improves roost detection performance from 47.0% mean average precision to 54.7%. Temporal information helps the model recognize the expanding pattern of roosts and filter false positives due to rain and static structures. Our system allowed the annotation of 15,628 roost signatures with 64,620 single-frame detections in 612,786 radar scans with 183.6 total hours of human screening, or 1.08 seconds per radar scan. C_LIO_LIOur AI-assisted system provides research-quality roost data with far less human effort than manual annotation of radar scans. The data contains critical information about the phenology and population trends of swallows and martins, a declining group of aerial insectivores. Our successful deployment to collect historical data for 8% of the radar stations in the contiguous US lays the groundwork for continentscale analysis of swallow roosts, and provides a starting point for analysis of other family-specific phenomena in weather radar, such as bat roosts and mayfly hatches. C_LI

ecology↗

bioRxiv2022

Pannexin 3 channels regulate architecture, adhesion, barrier function and inflammation in the skin

The channel-forming glycoprotein Pannexin 3 (PANX3) functions in cutaneous wound healing and keratinocyte differentiation, but its role in skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3 knockout mice (KO) and found that KO dorsal skin showed sex-differences at different ages, but generally had reduced dermal and hypodermal areas compared to aged-matched controls. Transcriptomic analysis of KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared to WT, consistent with the inability of primary KO keratinocytes to adhere in culture, and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in KO epidermis and higher incidence of dermatitis in aged KO mice compared to wildtype controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion and inflammatory skin responses.

cell biology↗

bioRxiv2022

Membrane interactions and uncoating of Aichi virus, a picornavirus that lacks a VP4

Kobuviruses are an unusual and poorly characterised genus within the picornavirus family, and can cause gastrointestinal enteric disease in humans, livestock and pets. The human Kobuvirus, Aichi virus (AiV) can cause severe gastroenteritis and deaths in children below the age of five years, however this is a very rare occurrence. During the assembly of most picornaviruses (e.g. poliovirus, rhinovirus and foot-and-mouth disease virus), the capsid precursor protein VP0 is cleaved into VP4 and VP2. However, Kobuviruses retain an uncleaved VP0. From studies with other picornaviruses, it is known that VP4 performs the essential function of pore formation in membranes, which facilitates transfer of the viral genome across the endosomal membrane and into the cytoplasm for replication. Here, we employ genome exposure and membrane interaction assays to demonstrate that pH plays a critical role in AiV uncoating and membrane interactions. We demonstrate that incubation at low pH alters the exposure of hydrophobic residues within the capsid, enhances genome exposure and enhances permeabilisation of model membranes. Furthermore, using peptides we demonstrate that the N-terminus of VP0 mediates membrane pore formation in model membranes, indicating that this plays an analogous function to VP4. ImportanceTo initiate infection, viruses must enter a host cell and deliver their genome into the appropriate location. The picornavirus family of small non-enveloped RNA viruses includes significant human and animal pathogens and are also models to understand the process of cell entry. Most picornavirus capsids contain the internal protein VP4, generated from cleavage of a VP0 precursor. During entry, VP4 is released from the capsid. In enteroviruses this forms a membrane pore, which facilitates genome release into the cytoplasm. Due to high levels of sequence similarity, it is expected to play the same role for other picornaviruses. Some picornaviruses, such as Aichi virus, retain an intact VP0, and it is unknown how these viruses re-arrange their capsids and induce membrane permeability in the absence of VP4. Here we have used Aichi virus as a model VP0 virus to test for conservation of function between VP0 and VP4. This could enhance understanding of pore function and lead to development of novel therapeutic agents that block entry.

microbiology↗

bioRxiv2021

Fluidics System for Resolving Concentration-Dependent Effects of Dissolved Gases on Tissue Metabolism

Oxygen (O2) and other dissolved gases such as the gasotransmitters H2S, CO and NO affect cell metabolism and function. To evaluate effects of dissolved gases on processes in tissue, we developed a fluidics system that controls dissolved gases while simultaneously measuring parameters of electron transport, metabolism and secretory function. We use pancreatic islets, retina and liver to highlight its ability to assess effects of O2 and H2S. Protocols aimed at emulating hypoxia-reperfusion conditions resolved a previously unrecognized transient spike in O2 consumption rate (OCR) following replenishment of O2, and tissue-specific recovery of OCR following hypoxia. The system revealed both inhibitory and stimulatory effects of H2S on insulin secretion rate from isolated islets. The unique ability of this new system to quantify metabolic state and cell function in response to precise changes in dissolved gases provides a powerful platform for cell physiologists to study a wide range of disease states.

cell biology↗

bioRxiv2020

Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform

Reverse genetics has been an indispensable tool revolutionising our insights into viral pathogenesis and vaccine development. Large RNA virus genomes, such as from Coronaviruses, are cumbersome to clone and to manipulate in E. coli hosts due to size and occasional instability1-3. Therefore, an alternative rapid and robust reverse genetics platform for RNA viruses would benefit the research community. Here we show the full functionality of a yeast-based synthetic genomics platform for the genetic reconstruction of diverse RNA viruses, including members of the Coronaviridae, Flaviviridae and Paramyxoviridae families. Viral subgenomic fragments were generated using viral isolates, cloned viral DNA, clinical samples, or synthetic DNA, and reassembled in one step in Saccharomyces cerevisiae using transformation associated recombination (TAR) cloning to maintain the genome as a yeast artificial chromosome (YAC). T7-RNA polymerase has been used to generate infectious RNA, which was then used to rescue viable virus. Based on this platform we have been able to engineer and resurrect chemically-synthetized clones of the recent epidemic SARS-CoV-24 in only a week after receipt of the synthetic DNA fragments. The technical advance we describe here allows to rapidly responding to emerging viruses as it enables the generation and functional characterization of evolving RNA virus variants - in real-time - during an outbreak.

microbiology↗

bioRxiv2020

Effectiveness of protected areas in conserving tropical forest birds

Protected areas are the cornerstones of global biodiversity conservation efforts1,2, but to fulfil this role they must be effective at conserving the ecosystems and species that occur within their boundaries. This is particularly imperative in tropical forest hotspots, regions that concentrate a major fraction of the worlds biodiversity while also being under intense human pressure3-5. But these areas strongly lack adequate monitoring datasets enabling to contrast biodiversity in protected areas with comparable unprotected sites6,7. Here we take advantage of the worlds largest citizen science biodiversity dataset - eBird8 - to quantify the extent to which protected areas in eight tropical forest biodiversity hotspots are effective at retaining bird diversity, and to understand the underlying mechanisms. We found generally positive effects of protection on the diversity of bird species that are forest-dependent, endemic to the hotspots, or threatened or Near Threatened, but not on overall bird species richness. Furthermore, we show that in most of the hotspots examined this is driven by protected areas preventing both forest loss and degradation. Our results support calls for increasing the extent and strengthening the management efforts within protected areas to reduce global biodiversity loss9-11.

ecology↗

bioRxiv2019

DeepInsight: A general framework for interpreting wide-band neural activity

AO_SCPLOWBSTRACTC_SCPLOWRapid progress in technologies such as calcium imaging and electrophysiology has seen a dramatic increase in the size and extent of neural recordings. Even so, interpretation of this data often depends on manual operations and requires considerable knowledge about the nature of the representation. Decoding provides a means to infer the information content of such recordings but typically requires highly processed data and prior knowledge of the encoding scheme. Here, we developed a deep-learning-framework able to decode sensory and behavioural variables directly from wide-band neural data. The network requires little user input and generalizes across stimuli, behaviours, brain regions, and recording techniques. Once trained, it can be analysed to determine elements of the neural code that are informative about a given variable. We validated this approach using data from rodent auditory cortex and hippocampus, identifying a novel representation of head direction encoded by putative CA1 interneurons.

neuroscience↗

bioRxiv2019

Beyond Conventional Models: Recreating the Initiation, Evolution, and Genome of GBM

BackgroundImagining ways to prevent or treat glioblastoma (GBM) have been hindered by a lack of understanding of its pathogenesis. Although PDGF-AA overexpression may be an early event, critical details of the core biology are lacking. Existing PDGF-driven models replicate its microscopic appearance but not the genomic architecture characteristic of the human disease. Here we report a new model of GBM that overcomes this barrier to authenticity. MethodsUsing a method developed to study neural stem cells, we investigated the effects of PDGF-AA on subventricular zone (SVZ) cells, the putative cell of origin of GBM. We micro-dissected SVZ tissue from p53-null and wild-type adult mice, established primary cultures in media supplemented with PDGF-AA, and assessed cell viability, proliferation, genome stability, and tumour forming potential. ResultsCounterintuitive to its canonical role as a growth factor, we observed immediate and massive death of SVZ cells in PDGF-AA. Wild-type cells did not survive in PDGF-AA. However, a small fraction of null cells evaded apoptosis, displayed attenuated proliferation, gradually accumulated whole chromosome gains and losses, and, signalled by sudden rapid proliferation and growth factor independence, became tumorigenic in immune-competent syngeneic mice. Transformed cells had an OPC-like profile, were resistant to PDGFR- inhibition, and harboured highly abnormal karyotypes similar to those seen in human GBMs. ConclusionThis model associates genome instability in SVZ cells with chronic exposure to PDGF-AA; it is the first model to replicate the genomic landscape of GBM and first in which the earliest phases of GBM can be directly observed. IMPORTANCE OF STUDYWe have developed a mouse model in which the initiation, evolution and genomic landscape of GBM can be thoroughly studied thus paving the way for ideas about how this deadly brain cancer might be prevented, interrupted at an occult stage, or treated with very different therapies.

cancer biology↗

bioRxiv2019

Immunity conferred by drug-cured experimental Trypanosoma cruzi infections is long-lasting and cross-strain protective

BackgroundThe long term and complex nature of Chagas disease in humans has restricted studies on vaccine feasibility. Animal models also have limitations due to technical difficulties in monitoring the extremely low parasite burden that is characteristic of chronic stage infections. Advances in imaging technology offer alternative approaches that circumvent these problems. Here, we describe the use of highly sensitive whole body in vivo imaging to assess the efficacy of recombinant viral vector vaccines and benznidazole-cured infections to protect mice from challenge with Trypanosoma cruzi.\n\nMethodology/Principal FindingsMice were infected with T. cruzi strains modified to express a red-shifted luciferase reporter. Using bioluminescence imaging, we assessed the degree of immunity to re-infection conferred after benznidazole-cure. Mice infected for 14 days or more, prior to the initiation of treatment, were highly protected from challenge with both homologous and heterologous strains (>99% reduction in parasite burden). Sterile protection against homologous challenge was frequently observed. This level of protection was considerably greater than that achieved with recombinant vaccines. It was also independent of the route of infection or size of the challenge inoculum, and was long-lasting, with no significant diminution in immunity after almost a year. When the primary infection was benznidazole-treated after 4 days (before completion of the first cycle of intracellular infection), the degree of protection was much reduced, an outcome associated with a minimal T. cruzi-specific IFN-{gamma}+ T cell response.\n\nConclusions/SignificanceOur findings suggest that a protective Chagas disease vaccine must have the ability to eliminate parasites before they reach organs/tissues, such as the GI tract, where once established, they become largely refractory to the induced immune response.\n\nAUTHOR SUMMARYChagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem throughout Latin America. Attempts to develop a vaccine have been hampered by technical difficulties in monitoring the extremely low parasite burden during the life-long chronic stage of infection. To circumvent these issues, we used highly sensitive bioluminescence imaging to assess the ability of recombinant viral vector vaccines and drug-cured infections to confer protection against experimental challenge in mice. We observed that drug-cured infections were much more effective than subunit vaccines, with many instances of sterile protection. Efficacy was independent of the route of infection or size of the challenge inoculum, and was undiminished after almost a year. In addition, drug-cured infections conferred a high level of cross-strain protection. The highly sensitive imaging procedures enabled us to visualise parasite distribution in mice where sterile protection was not achieved. This suggested that to confer sterile protection, vaccines must prevent the infection of organs/tissues that act as parasite reservoirs during the chronic stage. Once established at these sites, parasites become largely refractory to vaccine-induced elimination.

immunology↗

bioRxiv2018

Determination of host cell proteins constituting the molecular microenvironment of coronavirus replicase complexes by proximity-labeling

Positive-sense RNA viruses hijack intracellular membranes that provide niches for viral RNA synthesis and a platform for interactions with host proteins. However, little is known about host factors at the interface between replicase complexes and the host cytoplasm. We engineered a biotin ligase into a coronaviral replication/transcription complex (RTC) and identified >500 host proteins constituting the RTC microenvironment. siRNA-silencing of each RTC-proximal host factor demonstrated importance of vesicular trafficking pathways, ubiquitin-dependent and autophagy-related processes, and translation initiation factors. Notably, detection of translation initiation factors at the RTC was instrumental to visualize and demonstrate active translation proximal to replication complexes of several coronaviruses.\n\nCollectively, we establish a spatial link between viral RNA synthesis and diverse host factors of unprecedented breadth. Our data may serve as a paradigm for other positive-strand RNA viruses and provide a starting point for a comprehensive analysis of critical virus-host interactions that represent targets for therapeutic intervention.

microbiology↗

bioRxiv2016

Identifying Migrant Origins Using Genetics, Isotopes, and Habitat Suitability

O_LIIdentifying migratory connections across the annual cycle is important for studies of migrant ecology, evolution, and conservation. While recent studies have demonstrated the utility of high-resolution SNP-based genetic markers for identifying population-specific migratory patterns, the accuracy of this approach relative to other intrinsic tagging techniques has not yet been assessed.\nC_LIO_LIHere, using a straightforward application of Bayes' Rule, we develop a method for combining inferences from high-resolution genetic markers, stable isotopes, and habitat suitability models, to spatially infer the breeding origin of migrants captured anywhere along their migratory pathway. Using leave-one-out cross validation, we compare the accuracy of this combined approach with the accuracy attained using each source of data independently.\nC_LIO_LIOur results indicate that when each method is considered in isolation, the accuracy of genetic assignments far exceeded that of assignments based on stable isotopes or habitat suitability models. However, our joint assignment method consistently resulted in small, but informative increases in accuracy and did help to correct misassignments based on genetic data alone. We demonstrate the utility of the combined method by identifying previously undetectable patterns in the timing of migration in a North American migratory songbird, the Wilson's warbler.\nC_LIO_LIOverall, our results support the idea that while genetic data provides the most accurate method for tracking animals using intrinsic markers when each method is considered independently, there is value in combining all three methods. The resulting methods are provided as part of a new computationally-efficient R-package, GIAIH, allowing broad application of our statistical framework to other migratory animal systems.\nC_LI

ecology↗