An Empirical Bayesian Approach to Quantify Multi-Scale Spatial Structural Diversity in Remote Sensing Data

Landscape structure is as much a driver as a product of environmental and biological interactions and it manifests as scale-specific, but also as multi-scale patterns. Multi-scale structure affects processes on smaller and larger scales and its detection requires information from different scales to be combined. Herein, we propose a novel method to quantify multi-scale spatial structural diversity in continuous remote sensing data. We combined information from different extents with an empirical Bayesian model and we applied a new entropy metric and a value co-occurrence approach to capture heterogeneity. We tested this method on Normalized Difference Vegetation Index data in northern Eurasia and on simulated data and we also tested the effect of coarser pixel resolution. We find that multi-scale structural diversity can reveal itself as patches and linear landscape features, which persist or become apparent across spatial scales. Multi-scale line features reveal the transition zones between spatial regimes and multi-scale patches reveal those areas within transition zones where values are most different from each other. Additionally, spatial regimes themselves can be distinguished. We also find the choice of scale need not be informed by typical length-scales, which makes the method easy to implement. The proposed multi-scale approach can be applied to other contexts, following the roadmap we pave out in this study and using the tools available in the accompanying R package StrucDiv

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

An Empirical Bayesian Approach to Quantify Multi-Scale Spatial Structural Diversity in Remote Sensing Data

Landscape structure is as much a driver as a product of environmental and biological interactions and it manifests as scale-specific, but also as multi-scale patterns. Multi-scale structure affects processes on smaller and larger scales and its detection requires information from different scales to be combined. Herein, we propose a novel method to quantify multi-scale spatial structural diversity in continuous remote sensing data. We combined information from different extents with an empirical Bayesian model and we applied a new entropy metric and a value co-occurrence approach to capture heterogeneity. We tested this method on Normalized Difference Vegetation Index data in northern Eurasia and on simulated data and we also tested the effect of coarser pixel resolution. We find that multi-scale structural diversity can reveal itself as patches and linear landscape features, which persist or become apparent across spatial scales. Multi-scale line features reveal the transition zones between spatial regimes and multi-scale patches reveal those areas within transition zones where values are most different from each other. Additionally, spatial regimes themselves can be distinguished. We also find the choice of scale need not be informed by typical length-scales, which makes the method easy to implement. The proposed multi-scale approach can be applied to other contexts, following the roadmap we pave out in this study and using the tools available in the accompanying R package StrucDiv

Implementation of preemptive DNA sequence–based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study

The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping.Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response–related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug–gene pairs, were deposited preemptively in the Mayo electronic health record.For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping.Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources

Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations