This work defines the biophysical mechanism of phosphoregulation of microtubule binding by the kinetochore NDC80 complex. Conformational plasticity of the disordered tail of its Hec1 subunit integrates outputs from multiple phosphorylations to serve as a rheostat, providing a new paradigm for accurate regulation of microtubule-binding affinity.

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.

Best macular dystrophy (BMD) is an autosomal dominant form of macular degeneration, linked to mutations in the hBEST1 gene, which encodes the calcium activated chloride channel (CACC) bestrophin-1. The bestrophin family includes three additional members: hBEST2, 3 and 4. Because mutations in hBEST1 cause BMD, but a knockout does not, hBEST1 mutants have been suggested to exert a dominant negative effect through interaction with other CACCs. Using single molecule subunit counting and co-localization we find that each hBEST forms a homotetrameric channel. Despite considerable conservation among hBESTs, hBEST1 has little or no interaction with other hBESTs. Deletion and chimera analysis are being used to identify the portions of hBEST1 that allow assembly of like subunits and prevent assembly with other hBESTs. Our results suggest that the pathology caused by hBEST1 mutations is not due to assembly with other CACCs.

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.