Biology subjects

Easteal, S.

Publications and source records attributed to Easteal, S..

5 recordsLinked to original sources

bioRxiv2020

Mitochondrial pathway polygenic risk scores are associated with Alzheimer's Disease

INTRODUCTIONGenetic, animal and epidemiological studies involving biomolecular and clinical endophenotypes implicate mitochondrial dysfunction in Alzheimers disease (AD) pathogenesis. Polygenic risk scores (PRS) provide a novel approach to assess biological pathway-associated disease risk by combining the effects of variation at multiple, functionally related genes. METHODSWe investigated associations of PRS for genes involved in 12 mitochondrial pathways (pathway-PRS) related to AD in 854 participants from Alzheimers Disease Neuroimaging Initiative. RESULTSPathway-PRS for four mitochondrial pathways are significantly associated with increased AD risk: (i) response to oxidative stress (OR: 2.01 [95% Cl: 1.71, 2.37]); (ii) mitochondrial transport (OR: 1.81 [95% Cl: 1.55, 2.13]); (iii) hallmark oxidative phosphorylation (OR: 1.23 [95% Cl: 1.07, 1.41]); and (iv) mitochondrial membrane potential regulation (OR: 1.18 [95% Cl: 1.03, 1.36]). DISCUSSIONTherapeutic approaches targeting these pathways may have potential for modifying AD pathogenesis. Further investigation is required to establish a causal role for these pathways in AD pathology.

neuroscience↗

bioRxiv2020

PACIFIC: A lightweight deep-learning classifier of SARS-CoV-2 and co-infecting RNA viruses

Viral co-infections occur in COVID-19 patients, potentially impacting disease progression and severity. However, there is currently no dedicated method to identify viral co-infections in patient RNA-seq data. We developed PACIFIC, a deep-learning algorithm that accurately detects SARS-CoV-2 and other common RNA respiratory viruses from RNA-seq data. Using in silico data, PACIFIC recovers the presence and relative concentrations of viruses with >99% precision and recall. PACIFIC accurately detects SARS-CoV-2 and other viral infections in 63 independent in vitro cell culture and patient datasets. PACIFIC is an end-to-end tool that enables the systematic monitoring of viral infections in the current global pandemic.

bioinformatics↗

bioRxiv2019

MitoImpute: A Snakemake pipeline for imputation of mitochondrial genetic variants

BackgroundVariation in mitochondrial DNA (mtDNA) identified by genotyping microarrays or by sequencing only hypervariable regions of the genome may be insufficient to reliably assign mitochondrial genomes to phylogenetic lineages or haplogroups. This lack of resolution can limit functional and clinical interpretation of a substantial body of existing mtDNA data. To address this limitation, we developed and evaluated a method for imputing missing mtDNA single nucleotide variants (mtSNVs) that uses a large reference alignment of complete mtDNA sequences. The method and reference alignment are combined into a pipeline, which we call MitoImpute. ResultsWe aligned the sequences of 36,960 complete human mitochondrial genomes downloaded from GenBank, filtered and controlled for quality. These sequences were reformatted for use in imputation software, IMPUTE2. We assessed the imputation accuracy of MitoImpute by measuring haplogroup and genotype concordance in data from the 1,000 Genomes Project and the Alzheimers Disease Neuroimaging Initiative (ADNI). The mean improvement of haplogroup assignment in the 1,000 Genomes samples was 42.7% (Matthews correlation coefficient = 0.64). In the ADNI cohort, we imputed missing single nucleotide variants. ConclusionsThese results show that our reference alignment and panel can be used to impute missing mtSNVs in exiting data obtained from using microarrays, thereby broadening the scope of functional and clinical investigation of mtDNA. This improvement may be particularly useful in studies where participants have been recruited over time and mtDNA data obtained using different methods, enabling better integration of early data collected using less accurate methods with more recent sequence data.

genomics↗

bioRxiv2017

Global patterns of human ageing

Ageing is a common, but not universal1-3, degradation of biological systems. Ageing in human populations is marked by a highly constrained, log-linear acceleration of the probability of mortality with age4. This acceleration determines the onset and duration of human morbidity5 and the upper limits of human life. Recent studies have revealed remarkable taxonomic diversity in mortality-derived ageing rates1,3. However, the extent of intraspecific variation in ageing rates is assumed to be negligible2. Here we show the considerable diversity of human ageing rates, across 81,000 population-specific longitudinal measures of the ageing rate derived from 330 billion life-years of mortality data. These data reveal remarkable flexibility and unexpected trends in the pattern of human ageing. Populations with lo ...

developmental biology↗

bioRxiv2017

The dynamic upper limit of human lifespan

We respond to claims by Dong et al. that human lifespan is limited below 125 years. Using the log-linear increase in mortality rates with age to predict the upper limits of human survival we find, in contrast to Dong et al., that the limit to human lifespan is historically flexible and increasing. This discrepancy can be explained by Dong et al.s use of data with variable sample sizes, age-biased rounding errors, and log(0) instead of log(1) values in linear regressions. Addressing these issues eliminates the proposed 125-year upper limit to human lifespan.

physiology↗