Development And Operation Of Workflows, Tools And Infrastructure For Data Analysis Vladimir Kiselev @wikiselev Head of Programme Informatics Wellcome Sanger Institute 

• Cell Transcriptional Atlassing • Large scale imaging for spatial transcriptomics • Genomics study of cell lines (HipSci) • Computational methods development Cellular Genetics programme … 

What is our team doing? • Our team provides Computational/IT support for Cellular Genetics programme (~180 people) • We work on both upstream (processing raw data) and downstream (gaining biological insights) analysis pipelines • We interact with all of the faculty members in the programme • We move programme’s pipelines to the Cloud (Sanger introduced Flexible Compute Environment ~1.5 years ago) 

Why do we need the Cloud? or Computational challenges in academia 

Sequencing data growth • Data security • The time and cost of moving large datasets • Costs of redundant copies of the data • Data governance constraints (personally identifiable data) Increase in storage of next-generation sequencing data in the Sequence Read Archive (SRA) Cloud computing for genomic data analysis and collaboration, Ben Langmead & Abhinav Nellore, Nature Genetics Reviews, 2018 

Collaborative initiatives Cloud computing for genomic data analysis and collaboration, Ben Langmead & Abhinav Nellore, Nature Genetics Reviews, 2018 

Reproducibility Bespoke software • Hard to run at other sites • Dependencies problem Containers • Docker • Singularity BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods, Gorgolewski KJ et al., PLOS Computational Biology, 2017 

Moving to the cloud Flexible Compute Environment, Tim Cutts, Head of Scientific Computing at the Sanger Institute, 2016 

Last two decades at Sanger… 

Sanger classical setup • LSF batch scheduler (not free) • Software has to be manually installed (no Docker or Singularity support) • Dependencies • Custom bash scripts 

We use Nextflow 

Why Nextflow? Orchestration & Parallelisation Scalability & Portability Deployment & Reproducibility Flexible Compute Environment, Tim Cutts, Head of Scientific Computing at the Sanger Institute, 2016 Enabling Reproducible In-Silico Data Analysis with Nextflow, Paolo Di Tommaso, 2018 https://speakerdeck.com/pditommaso/enabling-reproducible-in-silico-data-analises-with-nextflow 

Nextflow Example bwa mem reference.fa sample.fq \ | samtools sort -o sample.bam Enabling Reproducible In-Silico Data Analysis with Nextflow, Paolo Di Tommaso, 2018 https://speakerdeck.com/pditommaso/enabling-reproducible-in-silico-data-analises-with-nextflow 

Nextflow Example process align_sample { input: file 'reference.fa' from genome_ch file 'sample.fq' from reads_ch output: file 'sample.bam' into bam_ch script: """ bwa mem reference.fa sample.fq \ | samtools sort -o sample.bam """ } Nextflow process: Enabling Reproducible In-Silico Data Analysis with Nextflow, Paolo Di Tommaso, 2018 https://speakerdeck.com/pditommaso/enabling-reproducible-in-silico-data-analises-with-nextflow 

Nextflow Example process align_sample { input: file 'reference.fa' from genome_ch file 'sample.fq' from reads_ch output: file 'sample.bam' into bam_ch script: """ bwa mem reference.fa sample.fq \ | samtools sort -o sample.bam """ } reads_ch = Channel.fromPath('data/*.fq') Implicit parallelism: Nextflow process: Enabling Reproducible In-Silico Data Analysis with Nextflow, Paolo Di Tommaso, 2018 https://speakerdeck.com/pditommaso/enabling-reproducible-in-silico-data-analises-with-nextflow 

Nextflow Example process align_sample { input: file 'reference.fa' from genome_ch file 'sample.fq' from reads_ch output: file 'sample.bam' into bam_ch script: """ bwa mem reference.fa sample.fq \ | samtools sort -o sample.bam """ } reads_ch = Channel.fromPath('data/*.fq') executor { name = 'lsf' queueSize = 400 } process { queue = 'normal' } Nextflow profile file: Implicit parallelism: Nextflow process: Enabling Reproducible In-Silico Data Analysis with Nextflow, Paolo Di Tommaso, 2018 https://speakerdeck.com/pditommaso/enabling-reproducible-in-silico-data-analises-with-nextflow 

Nextflow pipelines https://nf-co.re https://github.com/cellgeni 

The portability of Nextflow pipelines 

Nextflow Profiles nextflow run cellgeni/rnaseq --samplefile samples.txt --genome GRCh38 -profile lsf nextflow run cellgeni/rnaseq --samplefile samples.txt --genome GRCh38 -profile cloud 

We use Kubernetes cluster on the Cloud • Kubernetes cluster (open source) • Software in Docker containers • No dependencies problem • Scripts are encapsulated in Nextflow pipelines 

Why Kubernetes? 

Kubernetes • Hardware abstraction • Container orchestration • Nextflow integration Kubernetes in Action, Marko Luksa, Manning Publications, 2018 

Nextflow Integration • Benchmarking is needed • We are doing it • Can you share your experience? Nextflow documentation 

Kubernetes origins • In the early 2000s Google thinks of a better way of deploying and managing their software/infrastructure to scale globally • In ~2004 Google developed Borg and then Omega and kept it secret until 2014 • In 2014 Google introduced Kubernetes, an open-source system based on the experience gained through Borg, Omega • Kubernetes facilitates the deployment and serving of web applications 

Our web apps 

Simple web apps (with backend) https://github.com/cellgeni/FORECasT https://github.com/hemberg-lab/scmap-shiny 

Downstream analysis with JupyterHub • Jupyter Project (http://jupyter.org) • Multiuser • Provides containerized R/python/Julia environments • Rstudio server is included • Big compute in a browser window • We create templates for downstream analysis https://github.com/cellgeni/notebooks • Installation on Kubernetes cluster (one liner): helm upgrade --install jpt jupyterhub/jupyterhub --namespace jpt --version 0.7.0-beta.2 --values jupyter-config.yaml 

Downstream analysis with Galaxy • Expression group at EBI • Downstream analysis pipelines • Ready to be used • User-friendly • Installation on Kubernetes cluster is also a one liner https://github.com/ebi-gene-expression-group/container-galaxy-sc-tertiary 

Acknowledgements • Sanger IT • Helen Cousins • Theo Barber-Bany • Peter Clapham • Tim Cutts • Stijn van Dongen • Anton Khodak • Ruben Chazarra • Daniel Gaffney • Sarah Teichmann • Paolo Di Tomasso • Phil Ewels 

We are hiring! https://jobs.sanger.ac.uk/vacancies.html