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Hedman, K.

Publications and source records attributed to Hedman, K..

2 recordsLinked to original sources

Comparative evaluation of computational methods for reconstruction of human viral genomes

The increasing availability of viral sequences has led to the emergence of many optimized viral genome reconstruction tools. Given that the number of new tools is steadily increasing, it is complex to identify functional and optimized tools that offer an equilibrium between accuracy and computational resources as well as the features that each tool provides. In this paper, we surveyed open-source computational tools (including pipelines) used for human viral genome reconstruction, identifying specific characteristics, features, similarities, and dissimilarities between these tools. For quantitative comparison, we create an open-source reconstruction benchmark based on viral data. The benchmark was executed using both synthetic and real datasets. With the former, we evaluated the effects to the reconstruction process of using different human viruses with simulated mutation rates, contamination and mitochondrial DNA inclusion, and various coverage depths. Each reconstruction program was also evaluated using real datasets, demonstrating their performance in real-life scenarios. The evaluation measures include the identity, a Normalized Compression Semi-Distance, and the Normalized Relative Compression between the genomes before and after reconstruction, as well as metrics regarding the length of the genomes reconstructed, computational time and resources spent by each tool. The benchmark is fully reproducible and freely available at https://github.com/viromelab/HVRS.

bioinformatics↗

HHV-6B, HHV-7, and B19V Are Frequently Found DNA Viruses in the Human Thymus but Show No Definitive Link with Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder characterised by autoantibodies that target components of the neuromuscular junction, primarily the acetylcholine receptor (AChR), resulting in muscle weakness. The thymus plays a significant role in MG pathogenesis, particularly in patients under the age of 50, who display pathological alterations and possess elements conducive to autoimmune reactions. Although viral infections are suspected drivers of thymic pathogenesis, the exact aetiology of MG remains elusive. This study investigates the potential link between MG and DNA viruses within the thymus. Using targeted next-generation sequencing and quantitative PCR, we analysed the presence of human parvovirus B19 (B19V) and nine human herpesviruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6A, HHV-6B, HHV-7, and HHV-8) in fresh tissue samples from 19 non-thymomatous MG patients, 16 thymomas (3 with and 14 without MG), 41 normal thymus tissues, and 20 tonsils from healthy individuals. HHV-6B was the most common virus, found in over 50% of all tissue groups. B19V DNA was detected in 40% of adult control thymic tissue, 72% of MG thymus, 7.7% of non-MG thymoma, and 50% of tonsil samples. HHV-7 was present in 15-30% of thymus tissues and 95% of tonsils, while EBV was detected in less than 25% of all thymus samples but 85% of tonsils. In B19V seropositive individuals, B19V DNA was detected in 100% of thymic tissue from both MG patients and healthy individuals, except in thymomatous tissues, where it was found in only one of thirteen seropositive individuals. Immunohistochemistry for B19V protein expression did not show evident B19V VP1/VP2 protein expression, indicating dormant viral persistence. Laser capture microdissection (LCM) and RNAscope in situ hybridisation pinpointed B19V DNA localisation to the thymus medulla. This study is the first to demonstrate the persistence of various DNA viruses in the human thymus. However, neither B19V nor the nine human herpesviruses showed specific enrichment in MG thymic tissue compared to controls, suggesting that these viral infections are unlikely to be sole environmental triggers for MG.

immunology↗