Add SBX case study.

PiperOrigin-RevId: 799637820

Author: pichuan

README.md

@@ -23,6 +23,7 @@ DeepVariant supports germline variant-calling in diploid organisms.
 *   Complete Genomics
     [T7 case study](docs/deepvariant-complete-t7-case-study.md);
     [G400 case study](docs/deepvariant-complete-g400-case-study.md).
+*   Roche [SBX case study](docs/sbx-case-study.md) for SBX-D and SBX-Fast data.
 *   Pangenome-mapping-based case-study:
     [vg case study](docs/deepvariant-vg-case-study.md).
 *   RNA data for

docs/README.md

@@ -22,6 +22,7 @@
     [Mapped with VG](pangenome-aware-wgs-vg-case-study.md)
 *   Pangenome-aware DeepVariant WES:
     [Mapped with BWA](pangenome-aware-wes-bwa-case-study.md)
+*   [SBX case study](sbx-case-study.md)
 
 ## Visualization and analysis
 

docs/sbx-case-study.md

@@ -0,0 +1,125 @@
+# SBX case study for SBX-D and SBX-Fast data
+
+## Prepare environment
+
+### Tools
+
+[Docker](https://docs.docker.com/get-docker/) will be used to run DeepVariant
+and [hap.py](https://github.com/illumina/hap.py),
+
+### Download Reference
+
+We will be using GRCh38 for this case study.
+
+```bash
+mkdir -p reference
+
+FTPDIR=ftp://ftp.ncbi.nlm.nih.gov/genomes/all/GCA/000/001/405/GCA_000001405.15_GRCh38/seqs_for_alignment_pipelines.ucsc_ids
+
+curl ${FTPDIR}/GCA_000001405.15_GRCh38_no_alt_analysis_set.fna.gz | gunzip > reference/GRCh38_no_alt_analysis_set.fasta
+curl ${FTPDIR}/GCA_000001405.15_GRCh38_no_alt_analysis_set.fna.fai > reference/GRCh38_no_alt_analysis_set.fasta.fai
+```
+
+### Download T2T v1.1 truth for benchmarking
+
+We will benchmark our variant calls against T2T v1.1 truth for HG002.
+
+```bash
+mkdir -p benchmark
+
+HTTPDIR=https://storage.googleapis.com/deepvariant/case-study-testdata
+
+curl ${HTTPDIR}/GRCh38_HG2-T2TQ100-V1.1_smvar.vcf.gz > benchmark/GRCh38_HG2-T2TQ100-V1.1_smvar.vcf.gz
+curl ${HTTPDIR}/GRCh38_HG2-T2TQ100-V1.1_smvar.vcf.gz.tbi > benchmark/GRCh38_HG2-T2TQ100-V1.1_smvar.vcf.gz.tbi
+curl ${HTTPDIR}/GRCh38_HG2-T2TQ100-V1.1_smvar.benchmark.bed > benchmark/GRCh38_HG2-T2TQ100-V1.1_smvar.benchmark.bed
+```
+
+### Download GBZ built for GRCh38
+
+```bash
+mkdir -p input
+HTTPDIR=https://s3-us-west-2.amazonaws.com/human-pangenomics/pangenomes/freeze/freeze1/minigraph-cactus/hprc-v1.1-mc-grch38
+
+curl ${HTTPDIR}/hprc-v1.1-mc-grch38.gbz > input/hprc-v1.1-mc-grch38.gbz
+```
+
+### Download HG002 BAM
+
+Please download a SBX-D (or SBX-Fast) HG002 BAM and put it in your input dir.
+
+```bash
+# Download your HG002 BAM
+HG002_BAM=/input/your_HG002.bam  # This will be used in the command later.
+```
+
+### Download the model
+
+In this case study, we're calling variants on HG002 chr20, and we'll evaluate
+with T2T v1.1 truth. We'll use the "leave-out-HG001" model, which we also left
+out all chromosome 20 from training or tuning. Refer to the technical white
+paper for more details on all experiments.
+
+```bash
+mkdir -p model
+
+HTTPDIR=https://storage.googleapis.com/brain-genomics-public/research/sbx/2025/models/leave-out-HG001
+
+curl ${HTTPDIR}/model.ckpt.data-00000-of-00001 > model/model.ckpt.data-00000-of-00001
+curl ${HTTPDIR}/model.ckpt.index > model/model.ckpt.index
+curl ${HTTPDIR}/example_info.json > model/example_info.json
+```
+
+## Running DeepVariant with one command, on a CPU-only machine
+
+```bash
+mkdir -p output
+mkdir -p output/intermediate_results_dir
+
+BIN_VERSION="pangenome_aware_deepvariant-head784362481"
+
+sudo docker run \
+  -v "${PWD}/input":"/input" \
+  -v "${PWD}/output":"/output" \
+  -v "${PWD}/reference":"/reference" \
+  -v "${PWD}/model":"/model" \
+  --shm-size 12gb \
+  google/deepvariant:"${BIN_VERSION}" \
+  /opt/deepvariant/bin/run_pangenome_aware_deepvariant \
+  --model_type WGS \
+  --ref /reference/GRCh38_no_alt_analysis_set.fasta \
+  --reads "${HG002_BAM}" \
+  --pangenome /input/hprc-v1.1-mc-grch38.gbz \
+  --output_vcf /output/HG002.chr20.output.vcf.gz \
+  --output_gvcf /output/HG002.chr20.output.g.vcf.gz \
+  --num_shards $(nproc) \
+  --regions chr20 \
+  --intermediate_results_dir /output/intermediate_results_dir \
+  --customized_model /model/model.ckpt \
+  --make_examples_extra_args="alt_aligned_pileup=single_row,create_complex_alleles=true,enable_strict_insertion_filter=true,keep_legacy_allele_counter_behavior=true,keep_only_window_spanning_haplotypes=true,keep_supplementary_alignments=true,min_mapping_quality=0,normalize_reads=true,pileup_image_height_pangenome=100,pileup_image_height_reads=100,pileup_image_width=301,sort_by_haplotypes=true,trim_reads_for_pileup=true,vsc_min_fraction_indels=0.08,ws_min_base_quality=25" \
+  --postprocess_variants_extra_args="multiallelic_mode=product"
+```
+
+## Benchmark on chr20
+
+```bash
+mkdir -p happy
+
+sudo docker pull jmcdani20/hap.py:v0.3.12
+
+sudo docker run \
+  -v "${PWD}/benchmark":"/benchmark" \
+  -v "${PWD}/input":"/input" \
+  -v "${PWD}/output":"/output" \
+  -v "${PWD}/reference":"/reference" \
+  -v "${PWD}/happy:/happy" \
+  jmcdani20/hap.py:v0.3.12 \
+  /opt/hap.py/bin/hap.py \
+  /benchmark/GRCh38_HG2-T2TQ100-V1.1_smvar.vcf.gz \
+  /output/HG002.chr20.output.vcf.gz \
+  -f /benchmark/GRCh38_HG2-T2TQ100-V1.1_smvar.benchmark.bed \
+  -r /reference/GRCh38_no_alt_analysis_set.fasta \
+  -o /happy/happy.output \
+  --engine=vcfeval \
+  --pass-only \
+  -l chr20
+```