Merge pull request #7 from ave-dcd/revisions

Revisions

.requirements.txt

@@ -1,3 +1,4 @@
 pytest
 pyyaml
-jsonschema
+jsonschema
+ga4gh.gks.metaschema

concept_vocabulary.tsv

@@ -0,0 +1,65 @@
+Domain	Term	exactMapping(s)	Definition
+LibraryDeliveryMethod	adeno-associated virus transduction		Library delivery using adeno-associated virus transduction
+LibraryDeliveryMethod	chemical or heat shock transformation		Library delivery using chemical or heat shock transformation
+LibraryDeliveryMethod	chemical-based transfection		Library delivery using chemical-based transfection
+LibraryDeliveryMethod	electroporation		Library delivery using electroporation
+LibraryDeliveryMethod	lentivirus transduction		Library delivery using lentivirus transduction
+LibraryDeliveryMethod	nucleofection		Library delivery using nucleofection
+LibraryGenerationMechanism	base editor		A base editor mechanism of CRISPR/Cas mediated variant library generation
+LibraryGenerationMechanism	prime editor		A prime editor mechanism of CRISPR/Cas mediated variant library generation
+LibraryGenerationMechanism	nuclease		A nuclease mechanism of CRISPR/Cas mediated variant library generation
+LibraryGenerationSystem	AsCas12a		CRISPR/Cas mediated variant library generation by the AsCas12a system
+LibraryGenerationSystem	doped oligo synthesis		Doped oligo synthesis mediated variant library generation
+LibraryGenerationSystem	error-prone PCR		Error-prone Polymerase Chain Reaction (PCR) mediated variant library generation
+LibraryGenerationSystem	microarray synthesis		Microarray synthesis mediated variant library generation
+LibraryGenerationSystem	nicking mutagenesis		Nicking mutagenesis mediated variant library generation
+LibraryGenerationSystem	oligo pool synthesis		Oligo pool synthesis mediated variant library generation
+LibraryGenerationSystem	oligo-directed mutagenic PCR		Oligo-directed mutagenic Polymerase Chain Reaction (PCR) mediated variant library generation
+LibraryGenerationSystem	proprietary method		A proprietary method for variant library generation
+LibraryGenerationSystem	RfsCas13d		CRISPR/Cas mediated variant library generation by the RfsCas13d system
+LibraryGenerationSystem	SaCas9		CRISPR/Cas mediated variant library generation by the SaCas9 system
+LibraryGenerationSystem	site-directed mutagenesis		Site-directed mutagenesis mediated variant library generation
+LibraryGenerationSystem	SpCas9		CRISPR/Cas mediated variant library generation by the SpCas9 system
+LibraryIntegrationMechanism	episomal delivery		Library expression by episomal delivery
+LibraryIntegrationMechanism	extra-local construct insertion		Library integration at a designated integration site, e.g. with Landing Pad
+LibraryIntegrationMechanism	native locus replacement		Entire element replacement at the native locus (e.g. with integrases)
+LibraryIntegrationMechanism	plasmid (not integrated)		Expression of gene products from a non-integrating plasmid
+LibraryIntegrationMechanism	random locus viral integration		Intergration of a virus into a random locus
+LibraryIntegrationMechanism	transfection of RNA		Direct transfection of RNA
+PhenotypicAssayDimensionality	high-dimensional data		Assay with inherent high-dimensional data
+PhenotypicAssayDimensionality	combined functional data		Assay with multiple, combined functional readouts
+PhenotypicAssayDimensionality	single-dimensional data		Assay with a single-dimensional readout
+PhenotypicAssayMethod	binding assay	OBI:0001146	Phenotypic assay measuring binding (e.g. between two proteins)
+PhenotypicAssayMethod	bulk RNA-sequencing	OBI:0003090	Phenotypic assay using bulk RNA-sequencing
+PhenotypicAssayMethod	cell proliferation assay	OBI:0000891	Phenotypic assay measuring cell proliferation
+PhenotypicAssayMethod	systematic evolution of ligands by exponential enrichment assay	OBI:0002161	Phenotypic assay measuring evolution of ligands by exponential enrichment
+PhenotypicAssayMethod	flow cytometry assay	OBI:0000916	Phenotypic assay measuring fluorescence by flow cytometry
+PhenotypicAssayMethod	fluorescence in-situ hybridization (FISH) assay	OBI:0003094	Phenotypic assay using fluorescence in-situ hybridization (FISH)
+PhenotypicAssayMethod	imaging mass cytometry assay	OBI:0003096	Phenotypic assay using imaging mass cytometry
+PhenotypicAssayMethod	multiplexed fluorescent antibody imaging	OBI:0003091	Phenotypic assay using multiplexed fluorescent antibody imaging
+PhenotypicAssayMethod	promoter activity detection by reporter gene assay	OBI:0000913	Phenotypic assay measuring promoter activity using a reporter gene
+PhenotypicAssayMethod	single-cell imaging		Phenotypic assay using single cell imaging
+PhenotypicAssayMethod	single-cell RNA sequencing assay	OBI:0002631	Phenotypic assay using single-cell RNA sequencing
+PhenotypicAssayMethod	survival assessment assay	OBI:0000699	Phenotypic assay using a survival assessment assay
+PhenotypicAssayModelSystem	bacteria		Model system of bacteria (E. coli)
+PhenotypicAssayModelSystem	bacteriophage		Model system of bacteriophage
+PhenotypicAssayModelSystem	immortalized human cells		Model system of immortalized human cells (H. sapiens)
+PhenotypicAssayModelSystem	induced pluripotent stem cells from human female		Model system of induced pluripotent stem cells from human female
+PhenotypicAssayModelSystem	induced pluripotent stem cells from human male		Model system of induced pluripotent stem cells from human male
+PhenotypicAssayModelSystem	molecular display		Model system of molecular display
+PhenotypicAssayModelSystem	murine primary cells		Model system of mouse primary cells (M. musculus)
+PhenotypicAssayModelSystem	patient derived primary cells (e.g. T-cells, adipocytes)		Model system of patient derived primary cells (e.g. T-cells, adipocytes)
+PhenotypicAssayModelSystem	yeast		Model system of yeast (S. cerevisiae)
+PhenotypicAssayProfilingStrategy	barcode sequencing		Library profiling strategy of sequencing of a barcode associated with the variant library
+PhenotypicAssayProfilingStrategy	direct sequencing		Library profiling strategy of direct sequencing of the target variant library
+PhenotypicAssayProfilingStrategy	shotgun sequencing		Library profiling strategy of shotgun sequencing
+PhenotypicAssaySequencingMethod	multi-segment		Library sequencing method of sequencing of multiple segments using short or long reads
+PhenotypicAssaySequencingMethod	single-segment (long read)		Library sequencing method of sequencing of a single segment using long reads (e.g. Oxford Nanopore or PacBio)
+PhenotypicAssaySequencingMethod	single-segment (short read)		Library sequencing method of sequencing of a single segment using short reads (e.g. Illumina)
+VariantLibrary	base editor functionality		A base editor mechanism of a CRISPR/Cas variant library generation method
+VariantLibrary	prime editor functionality		A prime editor mechanism of a CRISPR/Cas variant library generation method
+VariantLibrary	wildtype nuclease functionality		A wildtype nuclease mechanism of a CRISPR/Cas variant library generation method
+VariantLibraryScope	coding		The protein-coding sequence of a gene
+VariantLibraryScope	intronic		Intronic sequence in between exons of a gene
+VariantLibraryScope	non-coding, other		Non-coding sequence corresponding to non-regulatory elements
+VariantLibraryScope	non-coding, regulatory		Non-coding sequence corresponding to regulatory elements (e.g. enhancers or promoters)

examples/Findlay_2018.yml

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+title: BRCA1 Saturation Genome Editing
+abstract: >-
+  Variants of uncertain significance fundamentally limit the clinical utility of genetic information. The challenge 
+  they pose is epitomized by BRCA1, a tumour suppressor gene in which germline loss-of-function variants predispose 
+  women to breast and ovarian cancer. Although BRCA1 has been sequenced in millions of women, the risk associated with 
+  most newly observed variants cannot be definitively assigned. Here we use saturation genome editing to assay 96.5% of 
+  all possible single-nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1. 
+  Functional effects for nearly 4,000 SNVs are bimodally distributed and almost perfectly concordant with established 
+  assessments of pathogenicity. Over 400 non-functional missense SNVs are identified, as well as around 300 SNVs that 
+  disrupt expression. We predict that these results will be immediately useful for the clinical interpretation of BRCA1 
+  variants, and that this approach can be extended to overcome the challenge of variants of uncertain significance in 
+  additional clinically actionable genes.
+document:
+  title: Accurate classification of BRCA1 variants with saturation genome editing
+  system:
+    Nature
+  date: "2018-09-12"
+  ref: https://doi.org/10.1038/s41586-018-0461-z
+datasets:
+  - system: MaveDB
+    accession: urn:mavedb:00000097
+    ref: https://mavedb.org/#/experiment-sets/urn:mavedb:00000097
+    description: processed scores, including scores for each replicate of each exon
+  - system: GEO
+    accession: GSE117159
+    ref: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE117159
+    description: raw sequencing data
+  - system: website
+    accession: https://sge.gs.washington.edu/BRCA1/
+    ref: https://sge.gs.washington.edu/BRCA1/
+    description: processed scores and visualizations hosted by the investigators
+variantLibrary:
+  scope:
+    type: coding
+  targetSequences:
+    - id: NM_007294.3
+      sequenceAlphabet: DNA
+  generationMethod:
+    type: endogenous locus library
+    system: SpCas9
+    mechanism: nuclease
+    description: Array-synthesized oligo pools (Agilent)
+  deliveryMethod:
+    type: other
+    description: Lipofection - TurboFectin
+phenotypicAssay:
+  dimensionality:
+    type: combined functional data
+  replication:
+    type: biological
+    description: two biological replicates were performed
+  method:
+    type: survival assessment assay
+  method:
+    type: bulk RNA-sequencing
+  relevance:
+    - system: https://www.omim.org/
+      code: "604370"
+      label: BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; BROVCA1
+    - system: https://www.omim.org/
+      code: "113705"
+      label: BRCA1 DNA REPAIR-ASSOCIATED PROTEIN; BRCA1
+    - system: https://mondo.monarchinitiative.org/
+      code: MONDO:0004984
+      label: basal-like breast carcinoma
+    - system: https://mondo.monarchinitiative.org/
+      code: MONDO:0011450
+      label: breast-ovarian cancer, familial, susceptibility to, 1
+  modelSystem:
+    type: immortalized human cells
+    description: HAP1
+    codings:
+      - system: https://www.ncbi.nlm.nih.gov/taxonomy
+        code: NCBI:txid9606
+        label: Homo sapiens
+  profilingStrategy: direct sequencing
+  sequencingReadType: multi-segment

examples/Matreyek_2018.yml

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+title: PTEN VAMP-seq
+abstract: >-
+  Determining the pathogenicity of genetic variants is a critical challenge, and functional assessment is often the 
+  only option. Experimentally characterizing millions of possible missense variants in thousands of clinically 
+  important genes requires generalizable, scalable assays. We describe variant abundance by massively parallel 
+  sequencing (VAMP-seq), which measures the effects of thousands of missense variants of a protein on intracellular 
+  abundance simultaneously. We apply VAMP-seq to quantify the abundance of 7,801 single-amino-acid variants of PTEN and 
+  TPMT, proteins in which functional variants are clinically actionable. We identify 1,138 PTEN and 777 TPMT variants 
+  that result in low protein abundance, and may be pathogenic or alter drug metabolism, respectively. We observe 
+  selection for low-abundance PTEN variants in cancer, and show that p.Pro38Ser, which accounts for ~10% of PTEN 
+  missense variants in melanoma, functions via a dominant-negative mechanism. Finally, we demonstrate that VAMP-seq is 
+  applicable to other genes, highlighting its generalizability.
+document:
+  title: >-
+    Multiplex assessment of protein variant abundance by massively parallel 
+    sequencing
+  system:
+    Nature Genetics
+  date: "2018-05-21"
+  ref: https://doi.org/10.1038/s41588-018-0122-z
+datasets:
+  - system: MaveDB
+    accession: urn:mavedb:00000013-a
+    ref: https://mavedb.org/#/experiments/urn:mavedb:00000013-a
+    description: processed scores, including scores for each replicate experiment
+  - system: BioProject
+    accession: PRJNA428380
+    ref: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA428380
+    description: raw sequencing data
+variantLibrary:
+  scope:
+    type: coding
+  targetSequences:
+    - sequence: "ATGACAGCCATCATCAAAGAGATCGTTAGCAGAAACAAAAGGAGATATCAAGAGGATGGA\
+        TTCGACTTAGACTTGACCTATATTTATCCAAACATTATTGCTATGGGATTTCCTGCAGAA\
+        AGACTTGAAGGCGTATACAGGAACAATATTGATGATGTAGTAAGGTTTTTGGATTCAAAG\
+        CATAAAAACCATTACAAGATATACAATCTTTGTGCTGAAAGACATTATGACACCGCCAAA\
+        TTTAATTGCAGAGTTGCACAATATCCTTTTGAAGACCATAACCCACCACAGCTAGAACTT\
+        ATCAAACCCTTTTGTGAAGATCTTGACCAATGGCTAAGTGAAGATGACAATCATGTTGCA\
+        GCAATTCACTGTAAAGCTGGAAAGGGACGAACTGGTGTAATGATATGTGCATATTTATTA\
+        CATCGGGGCAAATTTTTAAAGGCACAAGAGGCCCTAGATTTCTATGGGGAAGTAAGGACC\
+        AGAGACAAAAAGGGAGTAACTATTCCCAGTCAGAGGCGCTATGTGTATTATTATAGCTAC\
+        CTGTTAAAGAATCATCTGGATTATAGACCAGTGGCACTGTTGTTTCACAAGATGATGTTT\
+        GAAACTATTCCAATGTTCAGTGGCGGAACTTGCAATCCTCAGTTTGTGGTCTGCCAGCTA\
+        AAGGTGAAGATATATTCCTCCAATTCAGGACCCACACGACGGGAAGACAAGTTCATGTAC\
+        TTTGAGTTCCCTCAGCCGTTACCTGTGTGTGGTGATATCAAAGTAGAGTTCTTCCACAAA\
+        CAGAACAAGATGCTAAAAAAGGACAAAATGTTTCACTTTTGGGTAAATACATTCTTCATA\
+        CCAGGACCAGAGGAAACCTCAGAAAAAGTAGAAAATGGAAGTCTATGTGATCAAGAAATC\
+        GATAGCATTTGCAGTATAGAGCGTGCAGATAATGACAAGGAATATCTAGTACTTACTTTA\
+        ACAAAAAATGATCTTGACAAAGCAAATAAAGACAAAGCCAACCGATACTTTTCTCCAAAT\
+        TTTAAGGTGAAGCTGTACTTCACAAAAACAGTAGAGGAGCCGTCAAATCCAGAGGCTAGC\
+        AGTTCAACTTCTGTAACACCAGATGTTAGTGACAATGAACCTGATCATTATAGATATTCT\
+        GACACCACTGACTCTGATCCAGAGAATGAACCTTTTGATGAAGATCAGCATACACAAATT\
+        ACAAAAGTCTGA"
+      sequenceAlphabet: DNA
+  generationMethod:
+    type: in-vitro construct library
+    system: oligo-directed mutagenic PCR
+    integration: extra-local construct insertion
+    description: Integration using Tet-on landing pad system
+  deliveryMethod:
+    type: chemical or heat shock transformation
+phenotypicAssay:
+  dimensionality:
+    type: single-dimensional data
+  replication:
+    type: biological and technical
+    description: 8 biological replicate experiments were performed from three
+      different transfections (4, 3, and 1 experimental replicate for these
+      transfections). Technical replicates were performed as part of QC, but
+      the technical replicates were collapsed and analyzed as one experiment
+      after passing.
+  method:
+    type: flow cytometry assay
+    description: VAMP-seq
+  relevance:
+    - system: https://www.omim.org/
+      code: "601728"
+      label: PHOSPHATASE AND TENSIN HOMOLOG; PTEN
+    - system: https://www.omim.org/
+      code: "158350"
+      label: COWDEN SYNDROME 1; CWS1
+    - system: https://mondo.monarchinitiative.org/
+      code: MONDO:0017623
+      label: PTEN hamartoma tumor syndrome
+    - system: https://mondo.monarchinitiative.org/
+      code: MONDO:0017623
+      label: Cowden syndrome 1
+  modelSystem:
+    type: immortalized human cells
+    description: HEK 293T TetBxb1BFP
+    codings:
+      - system: https://www.ebi.ac.uk/ols/ontologies/clo
+        code: CLO:0037372
+        label: HEK293T cell
+      - system: https://www.ncbi.nlm.nih.gov/taxonomy
+        code: NCBI:txid9606
+        label: Homo sapiens
+  profilingStrategy: barcode sequencing
+  sequencingReadType: single-segment (short read)

examples/Seuma_2022.yml

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+title: Amyloid-Beta Deep Mutational Scan
+abstract: >-
+  Multiplexed assays of variant effects (MAVEs) guide clinical variant interpretation and reveal disease mechanisms. To 
+  date, MAVEs have focussed on a single mutation type–amino acid (AA) substitutions–despite the diversity of coding 
+  variants that cause disease. Here we use Deep Indel Mutagenesis (DIM) to generate a comprehensive atlas of diverse 
+  variant effects for a disease protein, the amyloid beta (Aβ) peptide that aggregates in Alzheimer's disease (AD) and 
+  is mutated in familial AD (fAD). The atlas identifies known fAD mutations and reveals that many variants beyond 
+  substitutions accelerate Aβ aggregation and are likely to be pathogenic. Truncations, substitutions, insertions, 
+  single- and internal multi-AA deletions differ in their propensity to enhance or impair aggregation, but likely 
+  pathogenic variants from all classes are highly enriched in the polar N-terminal region of Aβ. This comparative atlas 
+  highlights the importance of including diverse mutation types in MAVEs and provides important mechanistic insights 
+  into amyloid nucleation.
+document:
+  title: >-
+    An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta 
+    fibril nucleation.
+  system:
+    Nature Communications
+  date: "2022-11-18"
+  ref: https://doi.org/10.1038/s41467-022-34742-3
+datasets:
+  - system: MaveDB
+    accession: urn:mavedb:00000113-a
+    ref: https://mavedb.org/#/experiments/urn:mavedb:00000113-a
+    description: processed scores
+variantLibrary:
+  scope:
+    type: coding
+  targetSequences:
+    - id: ga4gh:SQ.upmBKNxvwSQPi9n6JMSkWimiVyhutErS
+      sha512t24u: upmBKNxvwSQPi9n6JMSkWimiVyhutErS
+      sequence: DAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIA
+      sequenceAlphabet: protein
+  generationMethod:
+    type: in-vitro construct library
+    system: oligo pool synthesis
+    integration: plasmid (not integrated)
+    description: Oligo pool synthesis, Twist Bioscience
+  deliveryMethod:
+    type: chemical or heat shock transformation
+phenotypicAssay:
+  dimensionality:
+    type: single-dimensional data
+  replication:
+    type: biological and technical
+    description: Three biological replicates (transformations) were performed and five technical replicate selections
+      were done for each. Sequencing was performed by combining six equimolar samples of each technical replicate.
+  method:
+    type: survival assessment assay
+    description: Survival assessment assay (growth in -adenine)
+  relevance:
+    - system: https://www.omim.org/
+      code: "104300"
+      label: ALZHEIMER DISEASE, FAMILIAL, 1; AD1
+    - system: https://www.omim.org/
+      code: "104760"
+      label: AMYLOID BETA A4 PRECURSOR PROTEIN; APP
+    - system: https://mondo.monarchinitiative.org/
+      code: MONDO:0004975
+      label: Alzheimer’s Disease
+  modelSystem:
+    type: yeast
+    description: Saccharomyces cerevisiae [psi-pin-]
+      (MATa ade1-14 his3 leu2-3,112 lys2 trp1 ura3-52)
+    codings:
+      - system: https://www.ncbi.nlm.nih.gov/taxonomy
+        code: NCBI:txid4932
+        label: Saccharomyces cerevisiae
+  profilingStrategy: direct sequencing
+  sequencingReadType: single-segment (short read)