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https://www.selleckchem.com/products/2-nbdg.html Single-cell barcoding technologies enable genome sequencing of thousands of individual cells in parallel, but with extremely low sequencing coverage ( less then 0.05×) per cell. While the total copy number of large multi-megabase segments can be derived from such data, important allele-specific mutations-such as copy-neutral loss of heterozygosity (LOH) in cancer-are missed. We introduce copy-number haplotype inference in single cells using evolutionary links (CHISEL), a method to infer allele- and haplotype-specific copy numbers in single cells and subpopulations of cells by aggregating sparse signal across hundreds or thousands of individual cells. We applied CHISEL to ten single-cell sequencing datasets of ~2,000 cells from two patients with breast cancer. We identified extensive allele-specific copy-number aberrations (CNAs) in these samples, including copy-neutral LOHs, whole-genome duplications (WGDs) and mirrored-subclonal CNAs. These allele-specific CNAs affect genomic regions containing well-known breast-cancer genes. We also refined the reconstruction of tumor evolution, timing allele-specific CNAs before and after WGDs, identifying low-frequency subpopulations distinguished by unique CNAs and uncovering evidence of convergent evolution.Proposed treatment targets for the management of inflammatory bowel disease (IBD) have moved beyond symptomatic improvement towards more objective end points, such as healing of the intestinal mucosa. This treat-to-target approach has been associated with improved disease outcomes such as diminished bowel damage, surgery and hospitalizations. Many patients with IBD require biologic therapy to achieve and maintain clinical and endoscopic remission, and antitumour necrosis factor antibodies remain the first-line biologic therapy in most areas of the world. Unfortunately, up to one-third of patients receiving this treatment are primary non-responders, and some patients that show
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