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Chapter 10: Cloud Execution: AWS Batch, S3 & AWS HealthOmics

Tested Stacks: GATK 4.6.1 Samtools 1.21 Nextflow 24.10 Seurat v5.1 Python 3.12
Prerequisites: Basic Linux CLI & Sequencing Formats
📚 Chapter 10 of 13 0% Course Completed

Chapter 10: Cloud Execution: AWS Batch, S3 & AWS HealthOmics

Cloud infrastructure allows genomics teams to scale from analyzing 5 samples to 50,000 samples instantaneously on elastic compute instances (EC2 Spot instances). Nextflow features deep, native integration with Amazon Web Services (AWS).

Architecture of Nextflow on AWS
  • Amazon S3: Serves as the central pipeline storage bucket (replacing the local POSIX filesystem).
  • AWS Batch: Automatically provisions and de-provisions Spot EC2 instances to run task containers.
  • AWS HealthOmics: Managed genomics service providing native Nextflow engine orchestration without managing servers.

1. Configuring AWS Batch in Nextflow

// nextflow.config AWS Batch profile
plugins {
    id 'nf-amazon'
}

profiles {
    awsbatch {
        process {
            executor = 'awsbatch'
            queue    = 'arn:aws:batch:us-east-1:123456789012:job-queue/genomics-spot-queue'
            container = 'quay.io/biocontainers/samtools:1.19.2--h50ea8bc_0'
        }

        aws {
            region = 'us-east-1'
            batch {
                cliPath = '/usr/local/bin/aws'
            }
        }

        workDir = 's3://my-genomics-bucket/work'
    }
}

2. Launching Workflows on AWS

# Run pipeline using S3 inputs and AWS Batch executor
nextflow run main.nf \
    -profile awsbatch \
    --input s3://my-genomics-bucket/data/samplesheet.csv \
    --outdir s3://my-genomics-bucket/results \
    -bucket-dir s3://my-genomics-bucket/work

3. Running Native Workflows in AWS HealthOmics

AWS HealthOmics executes Nextflow workflows as fully managed serverless runs with built-in audit trails, compliance tracking (HIPAA), and integrated biological reference stores.

⚠️

Common Pitfalls & Troubleshooting Checklist

  • Java Heap Exhaustion (GATK / Picard): If processes terminate with java.lang.OutOfMemoryError, set your environment variable explicitly: export _JAVA_OPTIONS="-Xmx16g -Djava.io.tmpdir=/tmp".
  • Index Timestamp Mismatch: If tools complain that a BAM index is missing or out of date, regenerate with samtools index -@ 4 sample.bam.
  • Conda Channel Conflicts: Avoid ABI incompatibilities between bioconda and conda-forge by setting strict priority: conda config --set channel_priority strict.
  • Chromosome Naming Contamination: Always verify whether reference FASTA headers use chr1 or 1; divergent naming causes silent alignment drops.
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