For most pathogens, vaccination reduces the spread of the infection and total number of cases; thus, public policy usually advocates maximizing vaccination coverage. We use simple mathematical models to explore how this may be different for pathogens, such as influenza, which exhibit strain variation. Our models predict that the total number of seasonal influenza infections is minimized at an intermediate (rather than maximal) level of vaccination, and, somewhat counter-intuitively, further increasing the level of the vaccination coverage may lead to higher number of influenza infections and be detrimental to the public interest. This arises due to the combined effects of: competition between multiple co-circulating strains; limited breadth of protection afforded by the vaccine; and short-term strain-transcending immunity following natural infection. The study highlights the need for better quantification of the components of vaccine efficacy and longevity of strain-transcending cross-immunity in order to generate nuanced recommendations for influenza vaccine coverage levels.
Human exome sequencing is a classical method used in most medical genetic applications. The leaders in the field are the manufacturers of enrichment kits based on hybridization of cRNA or cDNA biotinylated probes specific for a genomic region of interest. Recently, the platforms manufactured by the Chinese company MGI Tech have become widespread in Europe and Asia. The reliability and quality of the obtained data are already beyond any doubt. However, only a few kits compatible with these sequencers can be used for such specific tasks as exome sequencing. We developed our own solution for library pre-capture pooling and exome enrichment with Agilent probes. In this work, using a set of the standard benchmark samples from the Platinum Genome collection, we demonstrate that the qualitative and quantitative parameters of our protocol which we called “RSMU_exome” exceed those of the MGI Tech kit. Our protocol allows for identifying more SNV and indels, generates fewer PCR duplicates, enables pooling of more samples in a single enrichment procedure, and requires less raw data to obtain results comparable with the MGI Tech's protocol. The cost of our protocol is also lower than that of MGI Tech's solution.
Here we present the devised BC-store - a program for analyzing and selecting sets of barcodes for sequencing on platforms manufactured by MGI Tech (China). The app is available as an open source in Python3 and as a desktop version. The application allows analyzing the compatibility of barcodes on a single lane of a flow cell in a set in the case of equal and arbitrary fractions. In addition, with the help of this tool barcodes can be added to an existing set with custom share options. In this paper we describe how BC-store works for different tasks and consider the effectiveness of using BC-store in sequence lab routine tasks.
During the sequencing process, problems can occur with any device, including the MGISEQ-2000 (DNBSEQ-G400) platform. We encountered a power outage that resulted in a temporary shutdown of a sequencer in the middle of the run. Since barcode reading in MGISEQ-2000 takes place at the end of the run, it was impossible to use non-demultiplexed raw data. We decided to completely use up the same cartridge with reagents and flow cell loaded with DNB and started a new run in a shortened custom mode. We figured out how the MGISEQ-2000 converts preliminary data in .cal format into .fastq files and wrote a script named “Runcer-Necromacer” for merging .fastq files based on the analysis of their headers (available online: https://github.com/genomecenter/runcer-necromancer). Read merging proved to be possible because the MGISEQ-2000 flow cell has a patterned structure and each DNB has invariable coordinates on it, regardless of its position on the flow cell stage. We demonstrated the correctness of data merging by comparing sample analysis results with previously obtained .fastq files for them. Thus, we confirmed that it is possible to restart the device and save both parts of the interrupted run.
Human whole exome sequencing (WES) is now the standard for most medical genetics applica-tions worldwide. The leaders are manufacturers of enrichment kits that base their protocols on a hy-bridization approach using cRNA or cDNA biotinylated samples specific to regions of interest in the genome. Recently, platforms from the Chinese company MGI Tech have been successfully promoted in the markets of many countries in Europe and Asia. There is no longer any question about their re-liability and the quality of the data obtained. However, very few task-specific kits for WES, in par-ticular, are presented for these sequencers. We have developed our solution for library pre-capture pooling and exome enrichment using Agilent probes. In this work, we demonstrate on a set of stand-ard benchmark samples from the Platinum Genome Collection that our protocol, called RSMU_exome, is superior to the kit from MGI Tech in qualitative and quantitative terms. It allows detecting more SNVs and CNVs with superior sensitivity and specificity values, generates fewer PCR duplicates, allows more samples to be pooled in a single enrichment, and requires less raw data to produce results comparable to the MGI Tech solution. Also, our protocol is significantly cheaper than the kit from the Chinese manufacturer.
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