Biology subjects

Campbell, M.

Publications and source records attributed to Campbell, M..

At least 19 recordsLinked to original sources

bioRxiv2026

An amyloid-β/APP regulatory layer in human brown adipocyte recruitment identifies repurposable drugs for thermogenic fat expansion

Brown adipose tissue (BAT) increases energy expenditure but is scarce in adults, yet most strategies focus on activating existing thermogenic adipocytes rather than recruiting new ones. We integrate human single-nucleus transcriptomics with protein-interaction and knowledge-graph analyses to identify stage-specific, druggable programmes governing brown adipogenesis. This pipeline resolved four ordered transcriptional states and three transitions, revealing an amyloid-{beta}/APP regulatory layer and nominating APP as a central signalling hub. Most prioritised compounds altered differentiation or metabolic phenotype, several substantially. Phenserine (APP-lowering) and sacubitril (neprilysin inhibitor) promoted differentiation through distinct mechanisms and stages and could be combined sequentially for benefit. Phenserine increased differentiation across three human models and, in mice, expanded BAT mass and increased thermogenic capacity. Together, these findings reveal targetable control points in human brown adipocyte recruitment, nominate repurposable drugs for BAT expansion, and establish a generalisable framework coupling single-cell transcriptomics with network-based drug repurposing across staged biological systems.

cell biology↗

bioRxiv2026

Screening metatranscriptomes for ultrastable RNA secondary structures reveals hidden bacteriophages and novel capsid nanomaterials

Metatranscriptomics has transformed our view of RNA bacteriophage diversity, revealing vast numbers of single-stranded RNA (ssRNA) phages whose protein capsids can be engineered for biotechnology applications. However, many ssRNA phages remain hidden from current detection methods, which require protein-level similarity to known phages. Here we show that RNA structure provides an additional signal for the detection of ssRNA phages in metatranscriptomes, including hidden phages missed by prior protein-based methods. By computationally folding each contig and screening for exceptionally stable RNA secondary structures, we find evidence of thousands of previously unrecognized phages encoding novel coat proteins. We express a library of 12,000 such coat proteins in E. coli and find that most assemble into nuclease-resistant capsids. We determine the 3D structure of one such capsid by cryo-electron microscopy and demonstrate that it can be disassembled and reassembled in vitro to package heterologous RNA--a key step toward repurposing these particles as RNA delivery vehicles. We compile the newly discovered ssRNA phages with previously known ones into a database that contains sequence and structural information for over 460,000 unique RNA molecules and over 100,000 distinct coat proteins, providing a comprehensive resource for microbiology and nanomaterials research.

biochemistry↗

bioRxiv2026

OxBreaker: species-agnostic pipeline for the analysis of outbreaks using nanopore sequencing

Real-time genomic surveillance may mitigate the spread of health-care-associated infections, but whole-genome sequencing costs and the need for specialised expertise constrain its wide implementation in public health. Here we present OxBreaker, an automated and species-agnostic pipeline optimised for the high-resolution analysis of bacterial and plasmid genomes sequenced via Oxford Nanopore Technologies (ONT). OxBreaker streamlines the transition from raw reads to phylogenetic inference through automated reference selection and high-accuracy variant calling. It is accessible via a graphical user interface (GUI) that can be easily installed locally and operated by non-specialists. Benchmarking against technical and biological replicates of high-priority pathogens demonstrates high accuracy, with false positive variant rates reduced to 0-4 single-nucleotide polymorphisms (SNPs) for common species. We further validated the pipeline by accurately characterising previously published clonal and plasmid-mediated outbreaks, reproducing established phylogenies with improved accessibility. By providing a stable, scalable, open-source offline-compatible solution that matches the resolution of short-read platforms while maintaining the speed of long-read technology, OxBreaker is designed to facilitate the adoption of local, real-time genomic surveillance for frontline infection prevention and control.

genomics↗

bioRxiv2026

Hormone signaling and immune programs define differential endocrine responsiveness in high-risk breast tissue

Hormone therapies are frequently used to reduce breast cancer risk in individuals at increased risk for primary or subsequent disease; however, tissue-level responses to these therapies are heterogeneous and incompletely understood. Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) provides a non-invasive radiologic readout of breast tissue features associated with endocrine responsiveness and cancer risk. Although BPE is associated with hormonal exposure, a subset of patients with BPE do not show a response to preventive endocrine therapy and therefore may remain at increased breast cancer risk. In this study, we integrated single-nucleus RNA sequencing and spatial transcriptomics to define the determinants of endocrine responsiveness in the setting of BPE. We identify hormone-driven epithelial cells with high levels of estrogen signaling and endocrine responsiveness, together with immune-associated epithelial programs characterized by diminished luminal identity and increased expression of immune-modulatory pathways, including major histocompatibility complex (MHC) class II and CD74. Functional organoid assays validate that these epithelial states exhibit differential sensitivity to tamoxifen and demonstrate that inflammatory signals can induce immune-modulatory epithelial programs. Together, our findings identify hormone signaling and immune programs as key determinants of endocrine responsiveness in breast tissue and provide a biological basis for interpreting radiologic markers relevant to cancer prevention.

cancer biology↗

bioRxiv2025

A neuron type-specific microexon in Ank3/ankyrin-G modulates calcium activity and neuronal excitability

Recent studies have revealed many alternative exons differentially spliced across diverse neuron types in the mammalian brain, but their links to neuronal physiology remain unclear. Here we characterize a deeply conserved microexon E35a in Ank3 encoding ankyrin-G (AnkG), a multifaceted adaptor protein best known as a master organizer of the axon initial segment (AIS) and as a leading genetic risk factor for bipolar disorder. E35a is predominantly skipped in cortical glutamatergic neurons but included in cortical GABAergic neurons and cerebellar neurons, which is dictated by multiple neuronal splicing factors. In E35a-deletion mice we generated, interneurons show increased excitability and somatic Ca2+ activity, without disruption in AIS. Biochemical analyses suggest that E35a inclusion facilitates AnkG interaction with a protein complex involving inositol trisphosphate receptors (InsP3Rs) important for intracellular Ca2+ signaling. Alternative splicing therefore allows AnkG to modulate neuron type-specific excitability in addition to its ubiquitous pan-neuronal role in organizing the AIS.

neuroscience↗

bioRxiv2025

Endothelial tight junctions and cell-matrix adhesions reciprocally control blood-brain barrier integrity

Brain endothelial cells (ECs) rely on mechanical cues to provide a physical barrier that protects the brain. Yet how ECs integrate forces to establish and maintain the blood-brain barrier (BBB) remains poorly understood. Here, we show that the two main endothelial force-bearing systems, tight junctions and cell-matrix adhesions, reciprocally control BBB integrity. Using a combination of super-resolution imaging and biophysical techniques, we reveal increasing mechanical loads on cell-cell junctions vs. cell-matrix adhesions in human stem cell-derived ECs during BBB maturation. This force redistribution is enabled by cytoskeletal remodeling, a compacted pattern of the tight junction protein claudin-5, and the emergence of specialised perinuclear cell-matrix adhesions. Mechanistically, we find an inverse relationship between claudin-5 levels and the expression of key cell-matrix adhesion proteins zyxin and vinculin in vitro and in mice. Finally, we demonstrate that this mechanobiological signature associated with BBB maturation is reversed upon BBB dysfunction after seizures in mice and in human patients with temporal lobe epilepsy. Collectively, our findings establish a novel interplay between mechanoresponsive elements in brain ECs, with implications for BBB stabilisation therapy in epilepsy.

neuroscience↗

bioRxiv2024

The mitochondrial-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age

Aging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondrial-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. ELAM is proposed to restore mitochondrial bioenergetic function by stabilizing inner membrane structure and increasing oxidative phosphorylation coupling and efficiency. Although ELAM treatment effectively attenuates physiological declines in multiple tissues in rodent aging models, it remains unclear whether these functional improvements correlate with favorable changes in molecular biomarkers of aging. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function, coupled with post-treatment assessments of biological age and affected molecular pathways. We found that health status, as measured by frailty index, cardiac strain, diastolic function, and skeletal muscle force are significantly diminished with age, with skeletal muscle force changing in a sex-dependent manner. Conversely, ELAM mitigated frailty accumulation and was able to partially reverse these declines, as evidenced by treatment-induced increases in cardiac strain and muscle fatigue resistance. Despite these improvements, we did not detect statistically significant changes in gene expression or DNA methylation profiles indicative of molecular reorganization or reduced biological age in most ELAM-treated groups. However, pathway analyses revealed that ELAM treatment showed pro-longevity shifts in gene expression such as upregulation of genes involved in fatty acid metabolism, mitochondrial translation and oxidative phosphorylation, and downregulation of inflammation. Together, these results indicate that ELAM treatment is effective at mitigating signs of sarcopenia and heart failure in an aging mouse model, but that these functional improvements occur independently of detectable changes in epigenetic and transcriptomic age. Thus, some age-related changes in function may be uncoupled from changes in molecular biological age.

molecular biology↗

bioRxiv2024

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV

PurposePre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in pre-clinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with HIV. This study had three aims: 1.) Examine the relationship between IL-6 and the parasympathetic/vagal component of baroreflex sensitivity (BRS-V) in people with HIV; 2.) Determine if the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; 3.) Compare the burden of non-AIDS-related co-morbidities between immunotypes. Methods79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A).1 Levels of immune biomarkers were measured in all participants using the Target 96 Inflammation Panel on the Olink proteomics platform and immunotypes were identified using unbiased, non-negative matrix factorization. Mass cytometry (CyTOF) was completed on a subset of participants with and without autonomic neuropathy (N = 10). ResultsReduced BRS-V predicted higher levels of IL-6 (p=0.002). A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy characterized by deficits in sympathetic nervous system activity (aOR=4.7, p=0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities. ConclusionDeficits in the parasympathetic/cardiovagal and the sympathetic nervous system are associated with inflammation and disease burden in people living with HIV. Future longitudinal research is needed to examine causality.

immunology↗

bioRxiv2024

Gut and oral microbial community characterization from women with breast cancer, women with ductal carcinoma in situ, and healthy women reveals differences in gut but not oral microbiota

This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC versus healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified 5 bacterial guilds dominated by either Prevotella, Enterobacteriaceae, Akkermansia, Clostridiales, or Bacteroides. The Bacteroides and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes and very few differentially abundant taxa were observed. NMF analysis of the oral microbiota samples identified 7 guilds dominated by Veillonella, Prevotella, Gemellaceae, Haemophilus, Neisseria, Propionibacterium, and Streptococcus, however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota, but not oral microbiota, may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis. IMPORTANCEEmerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC) and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. These findings suggest that the oral microbiome is unlikely to be an effective risk marker for DCIS or breast cancer compared to the gut microbiome. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.

microbiology↗

bioRxiv2024

Reverse engineering neuron type-specific and type-orthogonal splicing-regulatory networks using single-cell transcriptomes

Cell type-specific alternative splicing (AS) enables differential gene isoform expression between diverse neuron types with distinct identities and functions. Current studies linking individual RNA-binding proteins (RBPs) to AS in a few neuron types underscore the need for holistic modeling. Here, we use network reverse engineering to derive a map of the neuron type-specific AS regulatory landscape from 133 mouse neocortical cell types defined by single-cell transcriptomes. This approach reliably inferred the regulons of 350 RBPs and their cell type-specific activities. Our analysis revealed driving factors delineating neuronal identities, among which we validated Elavl2 as a key RBP for MGE-specific splicing in GABAergic interneurons using an in vitro ESC differentiation system. We also identified a module of exons and candidate regulators specific for long- and short-projection neurons across multiple neuronal classes. This study provides a resource for elucidating splicing regulatory programs that drive neuronal molecular diversity, including those that do not align with gene expression-based classifications.

systems biology↗

bioRxiv2024

Protein structure, a genetic encoding for glycosylation

Unlike DNA, RNA, and protein biosynthesis, dogma describes glycosylation as primarily determined by intrinsic cellular limitations, such as glycosyltransferase expression and precursor availability. However, this cannot explain the commonly-observed differences between glycans on the same protein. By examining site-specific glycosylation on diverse human proteins, we detected associations between protein structure and glycan structure, broadly generalizable to human-expressed glycoproteins. Through structural analysis of site-specific glycosylation data, we found protein-sequence and structural features consistently correlated with specific glycan features. To quantify these relationships, we present a new amino acid substitution matrix describing "glycoimpact", i.e., the association of primary protein structure and glycosylation. High-glycoimpact amino acids co-evolve with glycosites, and glycoimpact is high when estimates of amino acid conservation and variant pathogenicity diverge. We report thousands of disease variants near glycosites with high-glycoimpact, including several with known links to aberrant glycosylation (e.g., Oculocutaneous Albinism, Jakob-Creutzfeldt disease, Gerstmann-Straussler-Scheinker, and Gauchers Disease). Finally, glycoimpact quantification is validated by studying oligomannose-complex glycan ratios on HIV ENV, differential sialylation on IgG3 Fc, differential glycosylation on SARS-CoV-2 Spike, and fucose-modulated function of a tuberculosis monoclonal antibody. Finally, to test the causality of protein-glycan associations, we created 5 glycoimpact-designed novel Rituximab variants, 4 of which substantially changed glycoprofiles as predicted. In all, we report that site-specific glycan biosynthesis is influenced by underlying protein structure, enabling glycan structure prediction and genetic sequence-guided glycoengineering.

genetics↗

bioRxiv2024

Hippocampal Signal Complexity and Rate-of-Change Predict Navigational Performance: Evidence from a Two-Week VR Training Program

The hippocampus is believed to be an important region for spatial navigation, helping to represent the environment and plan routes. Evidence from rodents has suggested that the hippocampus processes information in a graded manner along its long-axis, with anterior regions encoding coarse information and posterior regions encoding fine-grained information. Brunec et al. (2018) demonstrated similar patterns in humans in a navigation paradigm, showing that the anterior-posterior gradient in representational granularity and the rate of signal change exist in the human hippocampus. However, the stability of these signals and their relationship to navigational performance remain unclear. In this study, we conducted a two-week training program where participants learned to navigate through a novel city environment. We investigated inter-voxel similarity (IVS) and temporal auto-correlation hippocampal signals, measures of representational granularity and signal change, respectively. Specifically, we investigated how these signals were influenced by navigational ability (i.e., stronger vs. weaker spatial learners), training session, and navigational dynamics. Our results revealed that stronger learners exhibited a clear anterior-posterior distinction in IVS in the right hippocampus, while weaker learners showed less pronounced distinctions. Additionally, lower general IVS levels in the hippocampus were linked to better early learning. Successful navigation was characterized by faster signal change, particularly in the anterior hippocampus, whereas failed navigation lacked the anterior-posterior distinction in signal change. These findings suggest that signal complexity and signal change in the hippocampus are important factors for successful navigation, with IVS representing information organization and auto-correlation reflecting moment-to-moment updating. These findings support the idea that efficient organization of scales of representation in an environment may be necessary for efficient navigation itself. Understanding the dynamics of these neural signals provides insights into the mechanisms underlying navigational learning in humans.

neuroscience↗

bioRxiv2024

Comparison of CcrM-dependent methylation in Caulobacter crescentus and Brucella abortus by nanopore sequencing

Bacteria rely on DNA methylation for restriction-modification systems and epigenetic control of gene expression. Here, we use direct detection of methylated bases by nanopore sequencing to monitor global DNA methylation in Alphaproteobacteria, where use of this technique has not yet been reported. One representative of this order, Caulobacter crescentus, relies on DNA methylation to control cell cycle progression, but it is unclear whether other members of this order, such as Brucella abortus, depend on the same systems. We addressed these questions by first measuring CcrM-dependent DNA methylation in Caulobacter and show excellent correlation between nanopore-based detection and previously published results. We then directly measure the impact of Lon-mediated CcrM degradation on the epigenome, verifying that loss of Lon results in pervasive methylation. We also show that the AlkB demethylase has no global impact on DNA methylation during normal growth. Next, we report on the global DNA methylation in Brucella abortus for the first time and find that CcrM-dependent methylation is reliant on Lon but impacts the two chromosomes differently. Finally, we explore the impact of the MucR transcription factor, known to compete with CcrM methylation, on the Brucella methylome and share the results with a publicly available visualization package. Our work demonstrates the utility of nanopore-based sequencing for epigenome measurements in Alphaproteobacteria and reveals new features of CcrM-dependent methylation in a zoonotic pathogen. ImportanceDNA methylation plays an important role in bacteria to maintain genome integrity and regulate of gene expression. We used nanopore sequencing to directly measure methylated bases in Caulobacter crescentus and Brucella abortus. In Caulobacter, we showed that stabilization of the CcrM methyltransferase upon loss of the Lon protease results in prolific methylation and discovered that the putative methylase AlkB is unlikely to have a global physiological effect. We measured genome-wide methylation in Brucella for the first time, revealing a similar role for CcrM in cell-cycle methylation but a more complex regulation by the Lon protease than in Caulobacter. Finally, we show how the virulence factor MucR impacts DNA methylation patterns in Brucella.

microbiology↗

bioRxiv2024

Synchronization of Human Circadian Genes Between in vivo and Cultured Blood Samples

Transcriptomic studies of human circadian rhythm are limited in efficacy by the invasiveness of sampling. Studies of circadian dynamics should ideally use multiple blood samples drawn at regular intervals over the course of a day. This is difficult to achieve, particularly at night, without disrupting the very circadian rhythm that is being studied. We propose a method by which blood is drawn at a single initial timepoint, then cultured and repeatedly sampled over the course of a day. This method is minimally invasive to the subject. Our results demonstrate that the expression levels of circadian genes are more closely correlated between the cultured (ex vivo) cells and live (in vivo) samples than non-circadian genes, suggesting that this method can be used for effective circadian analysis.

genomics↗

bioRxiv2023

Arctos: Community-driven innovations for managing biodiversity and cultural collections

Museum collections house millions of objects and associated data records that document biological and cultural diversity. In recent decades, digitization efforts have greatly increased accessibility to these data, thereby revolutionizing interdisciplinary studies in evolutionary biology, biogeography, epidemiology, cultural change, and human-mediated environmental impacts. Curators and collection managers can make museum data as accessible as possible to scientists and learners by using a collection management system. However, selecting a system can be a challenging task. Here, we describe Arctos, a community solution for managing and accessing collections data for research and education. Specific goals are to: (1) Describe the core elements of Arctos for a broad audience with respect to the biodiversity informatics principles that enable high quality research; (2) Highlight the unique aspects of Arctos; (3) Illustrate Arctos as a model for supporting and enhancing the Digital Extended Specimen; and (4) Emphasize the role of the Arctos community for improving data discovery and enabling cross-disciplinary, integrative studies within a sustainable governance model. In addition to detailing Arctos as both a community of museum professionals and a collection database platform, we discuss how Arctos achieves its richly annotated data by creating a web of knowledge with deep connections between catalog records and derived or associated data. We also highlight the value of Arctos as an educational resource. Finally, we present a financial model of fiscal sponsorship by a non-profit organization, implemented in 2022, to ensure the long-term success and sustainability of Arctos. We attribute Arctos longevity of nearly three decades to its core development principles of standardization, flexibility, interdisciplinarity, and connectivity within a nimble development model for addressing novel needs and information types in response to changing technology, workflows, ethical considerations, and regulations.

bioinformatics↗

bioRxiv2023

Stereotypical hippocampal clustering predicts navigational success in virtualized real-world environments

Structural differences along the long-axis of the hippocampus have long been believed to underlie meaningful functional differences, such as the granularity of information processing. Recent findings show that data-driven parcellations of the hippocampus sub-divide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where subjects were trained to virtually navigate a novel neighborhood in a Google Street View-like environment over a two-week period. Subjects were scanned while navigating routes early in training and at the end of their two-week training. Using the 10-cluster map as the ideal template, we find that subjects who eventually learn the neighborhood well have hippocampal cluster-maps consistent with the ideal--even on their second day of learning--and their cluster mappings do not change over the two week training period. However, subjects who eventually learn the neighborhood poorly begin with hippocampal cluster-maps inconsistent with the ideal, though their cluster mappings become more stereotypical by the end of the two week training. Interestingly this improvement seems to be route specific as even after some early improvement, when a new route is navigated participants hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure, and instead is driven by a combination of anatomy, task, and importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral-axes.

neuroscience↗

bioRxiv2023

A parametric model for estimating the timing and intensity of animal migration

Animals of many different species, trophic levels, and life history strategies migrate, and the improvement of animal tracking technology allows ecologists to collect increasing amounts of detailed data on these movements. Understanding when animals migrate is important for managing their populations, but is still difficult despite modelling advancements. We designed a model that parametrically estimates the timing of migration from animal tracking data. Our model identifies the beginning and end of migratory movements as signaled by changes in step length and turning angle distributions. To this end, we can also use the model to estimate how an animals movement changes when it begins migrating. We tested our model on three datasets: migratory ferruginous hawks (Buteo regalis) in the Great Plains and barren-ground caribou (Rangifer tarandus groenlandicus) in northern Canada, and non-migratory brown bears (Ursus arctos) from the Canadian Arctic. We estimated the beginning and end of migration in caribou and hawks to the nearest day, while confirming a lack of migratory behaviour in the brown bear population. The flexibility of our modelling framework allowed us to assess intricacies associated with each dataset: long-term stopover behaviour in ferruginous hawks and a priori knowledge of caribou calving areas and behaviour. In addition to estimating when caribou and ferruginous hawks migrated, our model also identified differences in how the two populations migrated; ferruginous hawks achieved efficient migrations by increasing their movement rates while caribou migration was achieved through significant increases in directional persistence. Our approach is broadly applicable to many animal movement studies. We anticipate that rigorous assessment of migration metrics will aid understanding of both how and why animals move.

ecology↗

bioRxiv2022

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗