Search

Ancient environmental DNA (aeDNA) is becoming a powerful tool to gain insights about past ecosystems, overcoming the limitations of conventional fossil records. However, several methodological challenges remain, particularly for classifying the DNA to species level and conducting phylogenetic analysis. Current methods, primarily tailored for modern datasets, fail to capture several idiosyncrasies of aeDNA, including species mixtures from closely related species and ancestral divergence. We introduce soibean , a novel tool that utilizes mitochondrial pangenomic graphs for identifying species from aeDNA reads. It outperforms existing methods in accurately identifying species from multiple closely related sources within a sample, enhancing phylogenetic analysis for aeDNA. soibean employs a damage-aware likelihood model for precise identification at low coverage with a high damage rate. Additionally, we reconstructed ancestral sequences for soibean 's database to handle aeDNA that is highly diverged from modern references. soibean demonstrates effectiveness through simulated data tests and empirical validation. Notably, our method uncovered new empirical results in published datasets, including using porpoise whales as food in a Mesolithic community in Sweden, demonstrating its potential to reveal previously unrecognized findings in aeDNA studies. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39–77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117–164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed. Author summary: In addition to causing a pandemic in the human population, SARS-CoV-2 also infected farmed mink. In Denmark, after the first identification of infection in mink during June 2020, a decision was made in November 2020 to cull all the farmed mink. Within this outbreak, mink on 290 farms (out of about 1100 in the country) were found to have been infected. We showed, by analysis of the viruses from the mink, that the viruses on the farms were mainly of three different, but closely related, types (termed Clusters 2, 3 and 4) that shared certain distinctive features. Thus, we found that many outbreaks in mink resulted from transmission of the virus between mink farms. However, we identified that new introductions of other virus variants, presumably from infected humans, also occurred. Furthermore, we showed that spread of the virus from infected mink to humans also happened on multiple occasions. Thus, transmission of these viruses from humans to mink, mink to mink, from mink to humans and between humans were all observed. [ABSTRACT FROM AUTHOR]

Most heritable diseases are polygenic. To comprehend the underlying genetic architecture, it is crucial to discover the clinically relevant epistatic interactions (EIs) between genomic single nucleotide polymorphisms (SNPs) (1-3). Existing statistical computational methods for EI detection are mostly limited to pairs of SNPs due to the combinatorial explosion of higher-order EIs. With NeEDL (network-based epistasis detection via local search), we leverage network medicine to inform the selection of EIs that are an order of magnitude more statistically significant compared to existing tools and consist, on average, of five SNPs. We further show that this computationally demanding task can be substantially accelerated once quantum computing hardware becomes available. We apply NeEDL to eight different diseases and discover genes (affected by EIs of SNPs) that are partly known to affect the disease, additionally, these results are reproducible across independent cohorts. EIs for these eight diseases can be interactively explored in the Epistasis Disease Atlas (https://epistasis-disease-atlas.com). In summary, NeEDL demonstrates the potential of seamlessly integrated quantum computing techniques to accelerate biomedical research. Our network medicine approach detects higher-order EIs with unprecedented statistical and biological evidence, yielding unique insights into polygenic diseases and providing a basis for the development of improved risk scores and combination therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)