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Atta Leafcutter Ants are Fine-Scale Bioindicators of Geographic and Seasonal Climate Changes Across the Americas

AimWe develop Atta leafcutter-ants as bioindicators that respond at fine scales to geographic and seasonal climate changes in the Americas, thereby addressing the paucity of versatile insect bioindicator systems capable of monitoring climate in both Southern and Northern Hemispheres. LocationAmerican tropics and sub-tropics from latitudes S33.6{degrees} to N33.2{degrees}, with case studies from Colombia, Mexico, and southern USA. Time Period2012-2024. Taxon StudiedAtta leafcutter-ants. MethodsWe elucidate biogeographic patterns of mating-flight phenology of Atta leafcutter-ants across the entire Atta range from Uruguay/Argentina to the USA, using 2335 records of Atta reproductives from the community database iNaturalist, then ground-truth these patterns by comparison with (i) mating-flight records (n=806) from the Atta literature; and (ii) mating-flight observations (n=836) accumulated by a consortium of experts who have researched Atta for a combined 1000+ work-years. Onset of mating flights can be timed with great precision in Atta populations because mass-mating flights are synchronized and triggered by the first major rainfall of a rainy season. ResultsBiogeographic patterns in climate-dependent mating-flight phenologies recorded at iNaturalist are corroborated by observations accumulated in the literature and by Atta experts. Analyses reveal so-far unknown gradients in mating-flight phenology (e.g., Colombia to USA) that are correlated to geographic climate gradients, and season switches of mating flights from early to late in the year between proximate Atta populations (e.g., 200 kilometers apart), for example in the climatically complex Andean regions of Colombia. Regional differences in Atta mating-flight phenology correspond to temporal differences in rainfall between ecoregions of Colombia. Main ConclusionsAtta ants are tractable insect bioindicators to monitor climate impacts with detailed spatial and temporal resolution across a 9200-kilometer trans-equatorial transect in the Americas. We outline future research directions to explore climate-dependent biology using the continuously growing, and now ground-truthed, information at iNaturalist on Atta mating behavior.

ecology↗

Single-cell Multiome Analysis of Chromatin State and Transcriptome in the Human Basal Ganglia

The basal ganglia play essential roles in motor control, emotion, learning and reward processing. Their dysfunction contributes to many neurological and psychiatric disorders. However, the gene regulatory programs defining basal ganglia cell-type identity and function remain poorly understood, limiting interpretation of disease-associated non-coding variants. Here, we present the first single-cell multiome atlas of histone modifications and transcriptomes across eight basal ganglia regions from neurotypical adult human donors. Joint profiling reveals cell-type-specific deployment of active and repressive cis-regulatory elements and gene regulatory networks, and suggests a combinatorial homeobox transcription factor code underlying cell identity. Integration with matched spatial transcriptomic MERFISH data uncovers regional heterogeneity of epigenomic landscapes. Comparative analysis between human and mouse medium spiny neurons uncovers conservation of core gene regulatory features. This atlas interprets non-coding risk variants of neuropsychiatric disorders and supports the development of a deep learning model to predict gene regulation and functional effects of disease-associated variants. HIGHLIGHTSO_LIJoint single-cell profiling of transcriptomes and three histone modifications across eight human basal ganglia regions characterizes active and repressive chromatin states at cell-type resolution. C_LIO_LICell-type-specific gene regulatory programs decode combinatorial homeobox TF grammar governing the identity and diversification of basal ganglia neurons. C_LIO_LIIntergrative analyses link noncoding neuropsychiatric risk variants to specific cell types, regulatory elements, and candidate target genes. C_LIO_LIA sequence-to-function deep-learning model predicts gene regulation from DNA sequence and prioritizes functional disease-associated variants. C_LI

genomics↗

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations

INTRODUCTIONMulti-omics studies in Alzheimers disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD. METHODSTo bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTSWe generated multi-omics data and curated and harmonized phenotypic data from AA (n=306), LA (n=326), or AA and LA (n=4) brain donors plus Non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for AA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSIONInclusion of traditionally underrepresented groups in multi-omics studies is essential to discover the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

neuroscience↗

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics

A global genome database of all of Earths species diversity could be a treasure trove of scientific discoveries. However, regardless of the major advances in genome sequencing technologies, only a tiny fraction of species have genomic information available. To contribute to a more complete planetary genomic database, scientists and institutions across the world have united under the Earth BioGenome Project (EBP), which plans to sequence and assemble high-quality reference genomes for all [~]1.5 million recognized eukaryotic species through a stepwise phased approach. As the initiative transitions into Phase II, where 150,000 species are to be sequenced in just four years, worldwide participation in the project will be fundamental to success. As the European node of the EBP, the European Reference Genome Atlas (ERGA) seeks to implement a new decentralised, accessible, equitable and inclusive model for producing high-quality reference genomes, which will inform EBP as it scales. To embark on this mission, ERGA launched a Pilot Project to establish a network across Europe to develop and test the first infrastructure of its kind for the coordinated and distributed reference genome production on 98 European eukaryotic species from sample providers across 33 European countries. Here we outline the process and challenges faced during the development of a pilot infrastructure for the production of reference genome resources, and explore the effectiveness of this approach in terms of high-quality reference genome production, considering also equity and inclusion. The outcomes and lessons learned during this pilot provide a solid foundation for ERGA while offering key learnings to other transnational and national genomic resource projects.

genomics↗

Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.

genetics↗

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

AbstractWe assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain - resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.\n\nOne Sentence SummaryWe report a detailed genetic and genomic map of multiple sclerosis, and describe the role of putatively affected genes in the peripheral immune system and brain resident microglia.

genetics↗