Human Thymus single cell dissociation protocol - Teichmann Lab v1

This Protocol is intended for human Thymus single cell dissociation. It includes tissue preservation and handling, Enzymatic dissociation, FACS an MACS enrichments. Developed In the Teichmann lab at the Sanger institute, Wellcome Gemone Campus, UK VK, CS and JP contributed equally

Interim estimates of increased transmissibility, growth rate, and reproduction number of the Covid-19 B.1.617.2 variant of concern in the United Kingdom

This paper relates to data from the Wellcome Sanger Institute, UK, regarding Covid-19 genomic surveillance. We use a simple model to give point estimates of the effective reproduction numbers of the B.1.617.2 and B.1.1.7 lineages in England, from sequenced data as at 15 May 2021. Comparison with the estimated reproduction number of B.1.1.7 enables an estimate of the increased transmissibility of B.1.617.2. We conclude that it is almost certain that there is increased transmissibility that will rapidly lead to B.1.617.2 becoming the prevailing variant in the UK. The derived estimates of increased transmissibility have uncertainty relating to the actual distribution of the generation interval, but they do point, under present conditions of vaccination coverage and NPIs, to exponential growth of positive cases.

Exploiting the DepMap cancer dependency data using the depmap R package

The `depmap` package facilitates access in the R environment to the data from the DepMap project, a multi-year collaborative effort by the Broad Institute and Wellcome Sanger Institute, mapping genetic and chemical dependencies and other molecular biological measurements of over 1700 cancer cell lines. The 'depmap' package formats this data to simply the use of popular R data analysis and visualizing tools such as 'dplyr' and 'ggplot2'. In addition, the 'depmap' package utilizes 'ExperimentHub', storing versions of the DepMap data accessible from the Cloud, which may be selectively downloaded, providing a reproducible research framework to support exploiting this data. This paper describes a workflow demonstrating how to access and visualize the DepMap data in R using this package.

Launching the Tree of Life Gateway

The Tree of Life Gateway uses Genome Note publications to announce the completion of genomes assembled by the Tree of Life programme, based at the Wellcome Sanger Institute and involving numerous partner organisations and institutes. Tree of Life participates in the Darwin Tree of Life Project, which aims to sequence the genomes of all 70,000+ eukaryotic species in the Atlantic archipelago of Britain and Ireland, the Aquatic Symbiosis Genomics Project, which will sequence 1000 species involved in 500 symbioses between eukaryotic hosts and their microbial 'cobionts', and other initiatives, such as the Vertebrate Genome Project. These Genome Notes report the origins of ethically sourced samples used for sequencing, give the methods used to generate the sequence and use statistics and interactive figures to demonstrate the quality of the genome sequences. In addition to describing the production of these sequences, each Genome Note gives citeable credit to those who participated in producing the genome assembly and announces the availability of the data for reuse by all. It is through the use and reuse of this openly and publicly released data that we hope effective and lasting solutions to the ongoing biodiversity crisis can be found.

Sir John Edward Sulston CH. 27 March 1942—6 March 2018

In 2002 Sir John Sulston shared the Nobel Prize for Physiology or Medicine for his contribution to understanding the genetic control of cell fate during the development of the roundworm Caenorhabditis elegans . However, it was his position as one of the leaders of the international and publicly funded Human Genome Project that brought him to public prominence. Both his work on the worm cell lineage and his later commitment to genome sequencing as founding director of the Wellcome Trust Sanger Institute stemmed from his conviction that investing in large-scale data collection would have long-term benefits for future scientific discovery. He was a key figure in promoting the principle, now widely accepted, that genomic data should be universally and freely shared. After retiring from his post at the Sanger Institute he engaged with organizations with interests in biomedical ethics and global equality. He was a loyal and supportive colleague to many, delighting in the international collegiality of the ‘worm community’, of which he was a founding member.

A cancer pharmacogenomic screen powering crowd-sourced advancement of drug combination prediction

The effectiveness of most cancer targeted therapies is short lived since tumors evolve and develop resistance. Combinations of drugs offer the potential to overcome resistance, however the number of possible combinations is vast necessitating data-driven approaches to find optimal treatments tailored to a patient’s tumor. AstraZeneca carried out 11,576 experiments on 910 drug combinations across 85 cancer cell lines, recapitulating in vivo response profiles. These data, the largest openly available screen, were hosted by DREAM alongside deep molecular characterization from the Sanger Institute for a Challenge to computationally predict synergistic drug pairs and associated biomarkers. 160 teams participated to provide the most comprehensive methodological development and subsequent benchmarking to date. Winning methods incorporated prior knowledge of putative drug target interactions. For >60% of drug combinations synergy was reproducibly predicted with an accuracy matching biological replicate experiments, however 20% of drug combinations were poorly predicted by all methods. Genomic rationale for synergy predictions were identified, including antagonism unique to combined PIK3CB/D inhibition with the ADAM17 inhibitor where synergy is seen with other PI3K pathway inhibitors. All data, methods and code are freely available as a resource to the community.