// Copyright 2024 Google LLC.
//
// Licensed under the Apache License, Version 2.0 (the "License");
// you may not use this file except in compliance with the License.
// You may obtain a copy of the License at
//
// http://www.apache.org/licenses/LICENSE-2.0
//
// Unless required by applicable law or agreed to in writing, software
// distributed under the License is distributed on an "AS IS" BASIS,
// WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
// See the License for the specific language governing permissions and
// limitations under the License.
syntax = "proto3";
package google.gdm.gdmscience.alphagenome.v1main;
import "tensor.proto";
option go_package = "google.golang.org/genproto/googleapis/gdm/gdmscience/alphagenome/v1main;alphagenome";
option java_multiple_files = true;
option java_outer_classname = "DnaModelProto";
option java_package = "com.google.gdm.gdmscience.alphagenome.v1main";
// Message that represents a genomic interval.
message Interval {
// The chromosome name, e.g., "chr1".
string chromosome = 1;
// 0-based start position.
int64 start = 2;
// 0-based end position. Must be greater than or equal to start.
int64 end = 3;
// The strand of the interval.
Strand strand = 4;
}
// Message that represents a genomic variant/mutation.
message Variant {
// The chromosome name, e.g., "chr1".
string chromosome = 1;
// The 1-based position of the variant on the chromosome.
int64 position = 2;
// The reference base(s) at the variant position. Normally this corresponds to
// the sequence in the reference genome. Must only contain characters "ACGTN".
string reference_bases = 3;
// The alternate base(s) that replace the reference. For example:
// If sequence="ACT", position=2, reference_bases="C", alternate_bases="TG",
// then the alternate sequence would be "ATGT'.
string alternate_bases = 4;
}
// A single biological ontology term.
message OntologyTerm {
// The type of ontology this term belongs to.
OntologyType ontology_type = 1;
// The ID of the term within the ontology.
int64 id = 2;
}
// Message that represents a biological sample that is used in an experiment.
message Biosample {
// Biosample type matching ENCODE conventions.
BiosampleType type = 1;
// The name of the biosample, e.g. "T-cell".
string name = 2;
// Optional stage of the biosample, e.g. "adult".
optional string stage = 3;
}
// Message containing metadata for a gene score.
message GeneScorerMetadata {
// ENSEMBL gene identifier without version number, e.g. "ENSG00000100342".
string gene_id = 1;
// Optional HGNC gene symbol, e.g. "APOL1".
optional string name = 3;
// Optional strand of the gene.
optional Strand strand = 2;
// Optional gene biotype, e.g. "protein_coding" or "lncRNA".
optional string type = 4;
// Optional start position for junction scores.
optional int64 junction_start = 5;
// Optional end position for junction scores.
optional int64 junction_end = 6;
}
// Message containing metadata for a track.
message TrackMetadata {
// Name of the track.
string name = 1;
// Strand for the track.
Strand strand = 2;
// Ontology term for the track.
OntologyTerm ontology_term = 3;
// Biosample for the track.
Biosample biosample = 4;
// Optional assay for the track. e.g. "polyA plus RNA-seq".
optional string assay = 5;
// Optional histone mark for the track.
optional string histone_mark_code = 9;
// Optional transcription factor for the track.
optional string transcription_factor_code = 10;
// Optional GTEx tissue for the track.
optional string gtex_tissue = 8;
// Optional data source for the track. e.g. "encode".
optional string data_source = 11;
// Optional sequence reading endedness.
optional Endedness endedness = 12;
// Optional boolean indicating whether the track is genetically modified.
optional bool genetically_modified = 13;
// Optional mean of the non-zero values in the track.
optional float nonzero_mean = 14;
}
// Container for TrackMetadata.
message TracksMetadata {
// Ordered list of metadata for each track.
repeated TrackMetadata metadata = 1;
}
// Message containing metadata for a splice junctions.
message JunctionMetadata {
// Name of the junction track, e.g. "Brain_Cerebellum".
string name = 1;
// Ontology term for the junction track.
OntologyTerm ontology_term = 2;
// Biosample for the junction track.
Biosample biosample = 3;
// Optional GTEx tissue for the junction track.
optional string gtex_tissue = 4;
// Optional data source for the track. e.g. "encode".
optional string data_source = 5;
// Optional assay for the track. e.g. "polyA plus RNA-seq".
optional string assay = 6;
}
// Container for list of JunctionMetadata.
message JunctionsMetadata {
// Ordered list of metadata for each junction.
repeated JunctionMetadata metadata = 1;
}
// Message for storing track values and metadata.
message TrackData {
// Values for the track.
Tensor values = 1;
// Metadata for the track. The number of metadata elements must match the last
// dimension of the values tensor.
repeated TrackMetadata metadata = 2;
// Resolution of the track data in base pairs.
optional int64 resolution = 3;
// Optional Interval representing the genomic region.
Interval interval = 4;
}
// Message for storing splice junction values and metadata.
message JunctionData {
// Values for the splice junction for each track.
Tensor values = 1;
// Metadata for the splice junction. The number of elements must match the
// last dimension of the values tensor.
repeated JunctionMetadata metadata = 2;
// Predicted splice junctions. The number of elements must match the first
// dimensions of the values tensor.
repeated Interval junctions = 3;
}
// Message containing metadata for interval results.
message IntervalMetadata {
// Genomic interval.
Interval interval = 1;
// Track metadata for the interval prediction.
repeated TrackMetadata track_metadata = 2;
// Gene metadata for the interval prediction.
repeated GeneScorerMetadata gene_metadata = 3;
}
// Message for storing interval values and metadata.
message IntervalData {
// Values for the interval.
Tensor values = 1;
// Metadata for the interval.
IntervalMetadata metadata = 2;
}
// Message containing metadata for a variant prediction.
message VariantMetadata {
// Genomic variant.
Variant variant = 1;
// Track metadata for the variant prediction.
repeated TrackMetadata track_metadata = 2;
// Gene metadata for the variant prediction.
repeated GeneScorerMetadata gene_metadata = 3;
}
// Message for storing variant values and metadata.
message VariantData {
// Values for the variant.
Tensor values = 1;
// Metadata for the variant.
VariantMetadata metadata = 2;
}
// Message for storing model outputs for a single output type.
message Output {
// The type of output.
OutputType output_type = 1;
// The payload for the output.
oneof payload {
// Track data for the output. Used in all output types except
// OUTPUT_TYPE_SPLICE_JUNCTIONS.
TrackData track_data = 2;
// Raw predictions with no metadata.
Tensor data = 3;
// Junction data for the output. This is only set for
// OUTPUT_TYPE_SPLICE_JUNCTIONS.
JunctionData junction_data = 4;
}
}
// Message for storing score interval results.
message ScoreIntervalOutput {
// Score interval data.
IntervalData interval_data = 1;
}
// Message for storing score variant results.
message ScoreVariantOutput {
// Score variant data.
VariantData variant_data = 1;
}
// Interval scorer message for gene-mask scoring.
message GeneMaskIntervalScorer {
// Requested output type.
OutputType requested_output = 1;
// Requested width.
optional int64 width = 2;
// Requested aggregation type.
IntervalAggregationType aggregation_type = 3;
}
// Container message for all interval scorers.
message IntervalScorer {
// The interval scorer payload.
oneof scorer {
// Gene mask scorer.
GeneMaskIntervalScorer gene_mask = 1;
}
}
// Variant scorer message for center mask scoring.
message CenterMaskScorer {
// The width of the mask around the variant.
optional int64 width = 1;
// The aggregation type.
AggregationType aggregation_type = 2;
// Requested output type.
OutputType requested_output = 3;
}
// Variant scorer message for gene-mask scoring based on log fold change.
message GeneMaskLFCScorer {
// Requested output type.
OutputType requested_output = 1;
}
// Variant scorer message for gene-mask scoring based on active allele counts.
message GeneMaskActiveScorer {
// Requested output type.
OutputType requested_output = 1;
}
// Variant scorer message for gene-mask scoring for splicing.
message GeneMaskSplicingScorer {
// The width of the mask around the variant.
optional int64 width = 1;
// Requested output type.
OutputType requested_output = 2;
}
// Variant scorer message for polyadenylation QTLs (paQTLs).
message PolyadenylationScorer {}
// Variant scorer message for splice junction scoring.
message SpliceJunctionScorer {}
// Variant scorer message for contact map scoring.
message ContactMapScorer {}
// Container message for all variant scorers.
message VariantScorer {
// The variant scorer payload.
oneof scorer {
// Center mask scorer.
CenterMaskScorer center_mask = 1;
// Gene mask scorer based on log fold change.
GeneMaskLFCScorer gene_mask = 2;
// Gene mask scorer for splicing.
GeneMaskSplicingScorer gene_mask_splicing = 3;
// Polyadenylation scorer.
PolyadenylationScorer pa_qtl = 4;
// Splice junction scorer.
SpliceJunctionScorer splice_junction = 5;
// Contact map scorer.
ContactMapScorer contact_map = 6;
// Gene mask scorer based on active allele counts.
GeneMaskActiveScorer gene_mask_active = 7;
}
}
// Message containing metadata for an output type.
message OutputMetadata {
// The output type.
OutputType output_type = 1;
// The payload for the output metadata.
oneof payload {
// Track metadata for the output. Used in all output types except
// OUTPUT_TYPE_SPLICE_JUNCTIONS.
TracksMetadata tracks = 2;
// Junction metadata for the output. This is only set for
// OUTPUT_TYPE_SPLICE_JUNCTIONS.
JunctionsMetadata junctions = 3;
}
}
// Defines the possible strands for a DNA sequence.
enum Strand {
// Unspecified strand.
STRAND_UNSPECIFIED = 0;
// The forward strand (5' to 3')
STRAND_POSITIVE = 1;
// The reverse strand (3' to 5')
STRAND_NEGATIVE = 2;
// The strand is not specified.
STRAND_UNSTRANDED = 3;
}
// Supported ontology types.
enum OntologyType {
// Unspecified ontology type.
ONTOLOGY_TYPE_UNSPECIFIED = 0;
// Cell Line Ontology.
ONTOLOGY_TYPE_CLO = 1;
// Uber-anatomy ontology.
ONTOLOGY_TYPE_UBERON = 2;
// Cell Ontology.
ONTOLOGY_TYPE_CL = 3;
// Experimental Factor Ontology.
ONTOLOGY_TYPE_EFO = 4;
// New Term Requested.
ONTOLOGY_TYPE_NTR = 5;
}
// Biosample type matching ENCODE conventions. See
// https://www.encodeproject.org/profiles/biosample_type.
enum BiosampleType {
// Unspecified biosample type.
BIOSAMPLE_TYPE_UNSPECIFIED = 0;
// Primary cell sample.
BIOSAMPLE_TYPE_PRIMARY_CELL = 1;
// In-vitro differentiated cell sample.
BIOSAMPLE_TYPE_IN_VITRO_DIFFERENTIATED_CELLS = 2;
// Cell line sample.
BIOSAMPLE_TYPE_CELL_LINE = 3;
// Tissue sample.
BIOSAMPLE_TYPE_TISSUE = 4;
// Technical sample.
BIOSAMPLE_TYPE_TECHNICAL_SAMPLE = 5;
// Organoid sample.
BIOSAMPLE_TYPE_ORGANOID = 6;
}
// Enumeration of all the available types of outputs.
enum OutputType {
// Unspecified output type.
OUTPUT_TYPE_UNSPECIFIED = 0;
// ATAC-seq tracks capturing chromatin accessibility.
OUTPUT_TYPE_ATAC = 1;
// CAGE (Cap Analysis of Gene Expression) tracks capturing gene expression.
OUTPUT_TYPE_CAGE = 2;
// DNase I hypersensitive site tracks capturing chromatin accessibility.
OUTPUT_TYPE_DNASE = 3;
// RNA sequencing tracks capturing gene expression.
OUTPUT_TYPE_RNA_SEQ = 4;
// ChIP-seq tracks capturing histone modifications.
OUTPUT_TYPE_CHIP_HISTONE = 5;
// ChIP-seq tracks capturing transcription factor binding.
OUTPUT_TYPE_CHIP_TF = 6;
// Splice site tracks capturing donor and acceptor splice sites.
OUTPUT_TYPE_SPLICE_SITES = 7;
// Splice site usage tracks capturing the fraction of the time that each
// splice site is used.
OUTPUT_TYPE_SPLICE_SITE_USAGE = 8;
// Splice junction tracks capturing split read RNA-seq counts for each
// junction.
OUTPUT_TYPE_SPLICE_JUNCTIONS = 9;
// Contact map tracks capturing 3D chromatin contact probabilities.
OUTPUT_TYPE_CONTACT_MAPS = 11;
// Precision Run-On sequencing and capping, used to measure gene expression.
OUTPUT_TYPE_PROCAP = 12;
}
// Enumeration of all the available organisms. Values relate to the NCBI
// taxonomy ID.
enum Organism {
// Unspecified organism.
ORGANISM_UNSPECIFIED = 0;
// Human (Homo sapiens).
ORGANISM_HOMO_SAPIENS = 9606;
// Mouse (Mus musculus).
ORGANISM_MUS_MUSCULUS = 10090;
}
// Enum indicating the type of interval scorer aggregation.
enum IntervalAggregationType {
// Unspecified aggregation type.
INTERVAL_AGGREGATION_TYPE_UNSPECIFIED = 0;
// Mean across positions.
INTERVAL_AGGREGATION_TYPE_MEAN = 1;
// Sum across positions.
INTERVAL_AGGREGATION_TYPE_SUM = 2;
}
// Enum indicating the type of variant scorer aggregation.
enum AggregationType {
// Unspecified aggregation type.
AGGREGATION_TYPE_UNSPECIFIED = 0;
// Difference of means, i.e., mean(ALT) - mean(REF).
AGGREGATION_TYPE_DIFF_MEAN = 1;
// Difference of sums, i.e., sum(ALT) - sum(REF).
AGGREGATION_TYPE_DIFF_SUM = 2;
// Log ratio of sums, i.e., log(sum(ALT) / sum(REF)).
AGGREGATION_TYPE_LOG_RATIO_SUM = 3;
}
// Enum indicating read endedness.
enum Endedness {
// Unspecified.
ENDEDNESS_UNSPECIFIED = 0;
// Single end reads.
ENDEDNESS_SINGLE = 1;
// Paired end reads.
ENDEDNESS_PAIRED = 2;
}
