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Nonadditivity in fitness effects from two or more mutations, termed epistasis, can result in compensation of deleterious mutations or negation of beneficial mutations. Recent evidence shows the importance of epistasis in individual evolutionary pathways. However, an unresolved question in molecular evolution is how often and how significantly fitness effects change in alternative genetic backgrounds...
We present VGA, an accurate method for viral quasispecies assembly from ultra-deep sequencing data. The proposed method consists of a high-fidelity sequencing protocol and an accurate method for viral quasispecies assembly, referred to as Viral Genome Assembler (VGA). The proposed protocol is able to eliminate sequencing errors by using individual barcodes attached to the sequencing fragments. Results...
Pacific Biosciences (PacBio) sequencing is providing thousands of reads with the length up to 10,000 bases. In most cases this length is enough to cover entire region of interest however this technology has high (≈ 15%) error rate. We propose a method for viral haplotype reconstruction generalizes k-means clustering with Hamming distance and capable of handling up to 25% random errors. When applied...
Background The HIV-1 pandemic is not the result of a static pathogen but a large genetically diverse and dynamic viral population. The virus is characterized by a highly mutable genome rendering efforts to design a universal vaccine a significant challenge and drives the emergence of drug resistant variants upon antiviral pressure. Gaining a comprehensive understanding of the mutational tolerance...
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