A framework to assess quality and uncertainty in disaster loss data

There is a growing interest in the systematic and consistent collection of disasterloss data for different applications. Therefore, the collected data must follow a set oftechnical requirements to guarantee its usefulness. One of those requirements is theavailability of a measure of the uncertainty in the collected data to express its quality for agiven purpose. Many of the existing disaster loss databases do not provide such uncertainty/qualitymeasures due to the lack of a simple and consistent approach to expressuncertainty. After reviewing existing literature on the subject, a framework to express theuncertainty in disaster loss data is proposed. This framework builds on an existinguncertainty classification that was updated and combined with an existing method for datacharacterization. The proposed approach is able to establish a global score that reflects theoverall uncertainty in a certain loss indicator and provides a measure of its quality

Identifying differential regulatory control of APOE eP on African versus European haplotypes as potential therapeutic targets

We previously demonstrated that in Alzheimer's disease (AD) patients, European apolipoprotein E (APOE) epsilon 4 carriers express significantly more APOE epsilon 4 in their brains than African AD carriers. We examined single nucleotide polymorphisms near APOE with significant frequency differences between African and European/Japanese APOE epsilon 4 haplotypes that could contribute to this difference in expression through regulation. Two enhancer massively parallel reporter assay (MPRA) approaches were performed, supplemented with single fragment reporter assays. We used Capture C analyses to support interactions with the APOE promoter. Introns within TOMM40 showed increased enhancer activity in the European/Japanese versus African haplotypes in astrocytes and microglia. This region overlaps with APOE promoter interactions as assessed by Capture C analysis. Single variant analyses pinpoints rs2075650/rs157581, and rs59007384 as functionally different on these haplotypes. Identification of the mechanisms for differential regulatory function for APOE expression between African and European/Japanese haplotypes could lead to therapeutic targets for APOE epsilon 4 carriers

Transcriptomic characterization of a Puerto Rican Alzheimer disease cohort implicates convergent immune‐related pathways

BackgroundGenetic risk factors for Alzheimer disease (AD) demonstrate distinct effects across diverse ancestral populations. The ancestral heterogeneity (admixture) of Caribbean Hispanics from Puerto Rico (PR), makes studies of the PR population important in the discovery of ancestry‐specific factors in AD. To expand ongoing genomic investigations of AD in PR individuals, it is necessary to characterize functional downstream effects by studying gene expression and regulation. Here we characterized the differences in gene expression, splicing, and RNA editing of the protein coding transcriptome from peripheral blood in PR individuals. to identify case vs control differential expression, splicing, and RNA editing in this diverse population.MethodPoly‐A selected RNA was from peripheral whole blood of 76 PR individuals over the age of 65 (39 AD, 37 cognitively normal controls) was sequenced and analyzed with a standard bioinformatics pipeline. Differential expression between PR cases and controls was calculated using DESeq2, alternative splicing using LeafCutter software, and RNA editing with REDITools and linear models. All analyses were adjusted for sex, age, and sequencing coverage. For each analysis, pathway enrichment analysis of Gene Ontology Biological Processes and KEGG gene sets were used to identify underlying biological pathways.ResultA total of 761 genes (518 up‐regulated, 243 down‐regulated) were differentially expressed between PR AD and controls (adjusted p ≤ 0.05). At the transcript level, 561 genes had a significant (FDR ≤ 0.05) differential splicing event. We also identified 35,246 total RNA editing sites. While there was no significant difference globally, 422 sites in 159 genes showed nominally significant editing difference (p ≤ 0.05). These genes, isoforms, and RNA editing sites overlap little with previous investigations of the transcriptomes of Non‐Hispanic Whites and African‐American AD with only a few genes in common. However, pathway enrichment across all three PR transcriptomic analyses consistently reveals differences in both the adaptive and innate immune response pathways, consistent with other ancestries.ConclusionTranscriptomic analyses of diverse populations in AD, shows stark divergence at the single gene level. However, the convergence on immune molecular pathways suggest shared underlying disease etiology and the possibility of broad therapeutic options

Assessment of AD‐related plasma biomarkers in diverse ancestral populations

Background Plasma proteins as biomarkers for the differential diagnosis of AD from other similar neurodegenerative disorders, as well as the identification of preclinical AD, has recently been well supported across several large AD cohorts. However, these are composed primarily of individuals of non‐Hispanic European ancestry. Few studies have been performed in African‐American or Hispanic/Latinx AD populations to determine if plasma biomarkers are also useful in these populations. Given the differences in AD risk loci found across ancestries, the application of these biomarkers in diverse populations is not assured. Therefore, the aim of this study is to explore the utility of plasma biomarkers in AD, MCI and at‐risk family members from diverse ancestral backgrounds. Method As part of ongoing initiatives to understand AD in individuals of diverse ancestry, we are measuring the plasma level of biomarkers in a cohort of more than 3,000 individuals. This includes: 999 African Americans (248 AD cases, 591 controls, 160 MCI), 581 Puerto Ricans (223 AD cases, 208 controls, 150 MCI), 1052 Puerto Ricans in families (411 AD cases, 413 controls, 228 MCI), 98 Cubans (23 AD cases, 39 controls, 36 MCI), and 117 Peruvians (33 AD cases, 75 controls, 9 MCI). We will also have data on autopsy confirmed European AD cases (37) and a cohort of Amish individuals (∼400 AD cases, ∼200 MCI, and ∼500 controls). Plasma proteins tested are Aβ42, Aβ40, total Tau, and p‐Tau181 using Simoa chemistry assays (Quanterix HD‐X). All measurements are performed in duplicate and data analysis performed using HD‐X Analyzer Software v1.6. Result Measurement and analysis of biomarkers in this diverse dataset is currently underway and will be completed in a few months. These results will allow a direct comparison of biomarker analysis related to AD diagnosis between European, African, and Amerindian ancestries. Moreover, a family‐based design for over 1000 Puerto Rican individuals will be the first to identify potential heritable trends in biomarker levels. Conclusion This study is critical to being to understand how plasma biomarkers for AD may vary across diverse ancestries and whether previous findings will be generalizable and useful for all individuals, regardless of ancestry