// 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.genomics.v1;

import "google/api/annotations.proto";
import "google/protobuf/empty.proto";
import "google/protobuf/field_mask.proto";
import "google/protobuf/struct.proto";
import "google/protobuf/wrappers.proto";
import "google/rpc/status.proto";

option cc_enable_arenas = true;
option go_package = "google.golang.org/genproto/googleapis/genomics/v1;genomics";
option java_multiple_files = true;
option java_outer_classname = "AnnotationsProto";
option java_package = "com.google.genomics.v1";

// This service provides storage and positional retrieval of genomic
// reference annotations, including variant annotations.
service AnnotationServiceV1 {
  // Creates a new annotation set. Caller must have WRITE permission for the
  // associated dataset.
  //
  // The following fields are required:
  //
  //   * [datasetId][google.genomics.v1.AnnotationSet.dataset_id]
  //   * [referenceSetId][google.genomics.v1.AnnotationSet.reference_set_id]
  //
  // All other fields may be optionally specified, unless documented as being
  // server-generated (for example, the `id` field).
  rpc CreateAnnotationSet(CreateAnnotationSetRequest) returns (AnnotationSet) {
    option (google.api.http) = {
      post: "/v1/annotationsets"
      body: "annotation_set"
    };
  }

  // Gets an annotation set. Caller must have READ permission for
  // the associated dataset.
  rpc GetAnnotationSet(GetAnnotationSetRequest) returns (AnnotationSet) {
    option (google.api.http) = {
      get: "/v1/annotationsets/{annotation_set_id}"
    };
  }

  // Updates an annotation set. The update must respect all mutability
  // restrictions and other invariants described on the annotation set resource.
  // Caller must have WRITE permission for the associated dataset.
  rpc UpdateAnnotationSet(UpdateAnnotationSetRequest) returns (AnnotationSet) {
    option (google.api.http) = {
      put: "/v1/annotationsets/{annotation_set_id}"
      body: "annotation_set"
    };
  }

  // Deletes an annotation set. Caller must have WRITE permission
  // for the associated annotation set.
  rpc DeleteAnnotationSet(DeleteAnnotationSetRequest)
      returns (google.protobuf.Empty) {
    option (google.api.http) = {
      delete: "/v1/annotationsets/{annotation_set_id}"
    };
  }

  // Searches for annotation sets that match the given criteria. Annotation sets
  // are returned in an unspecified order. This order is consistent, such that
  // two queries for the same content (regardless of page size) yield annotation
  // sets in the same order across their respective streams of paginated
  // responses. Caller must have READ permission for the queried datasets.
  rpc SearchAnnotationSets(SearchAnnotationSetsRequest)
      returns (SearchAnnotationSetsResponse) {
    option (google.api.http) = {
      post: "/v1/annotationsets/search"
      body: "*"
    };
  }

  // Creates a new annotation. Caller must have WRITE permission
  // for the associated annotation set.
  //
  // The following fields are required:
  //
  // * [annotationSetId][google.genomics.v1.Annotation.annotation_set_id]
  // * [referenceName][google.genomics.v1.Annotation.reference_name] or
  //   [referenceId][google.genomics.v1.Annotation.reference_id]
  //
  // ### Transcripts
  //
  // For annotations of type TRANSCRIPT, the following fields of
  // [transcript][google.genomics.v1.Annotation.transcript] must be provided:
  //
  // * [exons.start][google.genomics.v1.Transcript.Exon.start]
  // * [exons.end][google.genomics.v1.Transcript.Exon.end]
  //
  // All other fields may be optionally specified, unless documented as being
  // server-generated (for example, the `id` field). The annotated
  // range must be no longer than 100Mbp (mega base pairs). See the
  // [Annotation resource][google.genomics.v1.Annotation]
  // for additional restrictions on each field.
  rpc CreateAnnotation(CreateAnnotationRequest) returns (Annotation) {
    option (google.api.http) = {
      post: "/v1/annotations"
      body: "annotation"
    };
  }

  // Creates one or more new annotations atomically. All annotations must
  // belong to the same annotation set. Caller must have WRITE
  // permission for this annotation set. For optimal performance, batch
  // positionally adjacent annotations together.
  //
  // If the request has a systemic issue, such as an attempt to write to
  // an inaccessible annotation set, the entire RPC will fail accordingly. For
  // lesser data issues, when possible an error will be isolated to the
  // corresponding batch entry in the response; the remaining well formed
  // annotations will be created normally.
  //
  // For details on the requirements for each individual annotation resource,
  // see
  // [CreateAnnotation][google.genomics.v1.AnnotationServiceV1.CreateAnnotation].
  rpc BatchCreateAnnotations(BatchCreateAnnotationsRequest)
      returns (BatchCreateAnnotationsResponse) {
    option (google.api.http) = {
      post: "/v1/annotations:batchCreate"
      body: "*"
    };
  }

  // Gets an annotation. Caller must have READ permission
  // for the associated annotation set.
  rpc GetAnnotation(GetAnnotationRequest) returns (Annotation) {
    option (google.api.http) = {
      get: "/v1/annotations/{annotation_id}"
    };
  }

  // Updates an annotation. Caller must have
  // WRITE permission for the associated dataset.
  rpc UpdateAnnotation(UpdateAnnotationRequest) returns (Annotation) {
    option (google.api.http) = {
      put: "/v1/annotations/{annotation_id}"
      body: "annotation"
    };
  }

  // Deletes an annotation. Caller must have WRITE permission for
  // the associated annotation set.
  rpc DeleteAnnotation(DeleteAnnotationRequest)
      returns (google.protobuf.Empty) {
    option (google.api.http) = {
      delete: "/v1/annotations/{annotation_id}"
    };
  }

  // Searches for annotations that match the given criteria. Results are
  // ordered by genomic coordinate (by reference sequence, then position).
  // Annotations with equivalent genomic coordinates are returned in an
  // unspecified order. This order is consistent, such that two queries for the
  // same content (regardless of page size) yield annotations in the same order
  // across their respective streams of paginated responses. Caller must have
  // READ permission for the queried annotation sets.
  rpc SearchAnnotations(SearchAnnotationsRequest)
      returns (SearchAnnotationsResponse) {
    option (google.api.http) = {
      post: "/v1/annotations/search"
      body: "*"
    };
  }
}

// An annotation set is a logical grouping of annotations that share consistent
// type information and provenance. Examples of annotation sets include 'all
// genes from refseq', and 'all variant annotations from ClinVar'.
message AnnotationSet {
  // The server-generated annotation set ID, unique across all annotation sets.
  string id = 1;

  // The dataset to which this annotation set belongs.
  string dataset_id = 2;

  // The ID of the reference set that defines the coordinate space for this
  // set's annotations.
  string reference_set_id = 3;

  // The display name for this annotation set.
  string name = 4;

  // The source URI describing the file from which this annotation set was
  // generated, if any.
  string source_uri = 5;

  // The type of annotations contained within this set.
  AnnotationType type = 6;

  // A map of additional read alignment information. This must be of the form
  // map<string, string[]> (string key mapping to a list of string values).
  map<string, google.protobuf.ListValue> info = 17;
}

// An annotation describes a region of reference genome. The value of an
// annotation may be one of several canonical types, supplemented by arbitrary
// info tags. An annotation is not inherently associated with a specific
// sample or individual (though a client could choose to use annotations in
// this way). Example canonical annotation types are `GENE` and
// `VARIANT`.
message Annotation {
  // The server-generated annotation ID, unique across all annotations.
  string id = 1;

  // The annotation set to which this annotation belongs.
  string annotation_set_id = 2;

  // The display name of this annotation.
  string name = 3;

  // The ID of the Google Genomics reference associated with this range.
  string reference_id = 4;

  // The display name corresponding to the reference specified by
  // `referenceId`, for example `chr1`, `1`, or `chrX`.
  string reference_name = 5;

  // The start position of the range on the reference, 0-based inclusive.
  int64 start = 6;

  // The end position of the range on the reference, 0-based exclusive.
  int64 end = 7;

  // Whether this range refers to the reverse strand, as opposed to the forward
  // strand. Note that regardless of this field, the start/end position of the
  // range always refer to the forward strand.
  bool reverse_strand = 8;

  // The data type for this annotation. Must match the containing annotation
  // set's type.
  AnnotationType type = 9;

  oneof value {
    // A variant annotation, which describes the effect of a variant on the
    // genome, the coding sequence, and/or higher level consequences at the
    // organism level e.g. pathogenicity. This field is only set for annotations
    // of type `VARIANT`.
    VariantAnnotation variant = 10;

    // A transcript value represents the assertion that a particular region of
    // the reference genome may be transcribed as RNA. An alternative splicing
    // pattern would be represented as a separate transcript object. This field
    // is only set for annotations of type `TRANSCRIPT`.
    Transcript transcript = 11;
  }

  // A map of additional read alignment information. This must be of the form
  // map<string, string[]> (string key mapping to a list of string values).
  map<string, google.protobuf.ListValue> info = 12;
}

message VariantAnnotation {
  message ClinicalCondition {
    // A set of names for the condition.
    repeated string names = 1;

    // The set of external IDs for this condition.
    repeated ExternalId external_ids = 2;

    // The MedGen concept id associated with this gene.
    // Search for these IDs at http://www.ncbi.nlm.nih.gov/medgen/
    string concept_id = 3;

    // The OMIM id for this condition.
    // Search for these IDs at http://omim.org/
    string omim_id = 4;
  }

  enum Type {
    TYPE_UNSPECIFIED = 0;

    // `TYPE_OTHER` should be used when no other Type will suffice.
    // Further explanation of the variant type may be included in the
    // [info][google.genomics.v1.Annotation.info] field.
    TYPE_OTHER = 1;

    // `INSERTION` indicates an insertion.
    INSERTION = 2;

    // `DELETION` indicates a deletion.
    DELETION = 3;

    // `SUBSTITUTION` indicates a block substitution of
    // two or more nucleotides.
    SUBSTITUTION = 4;

    // `SNP` indicates a single nucleotide polymorphism.
    SNP = 5;

    // `STRUCTURAL` indicates a large structural variant,
    // including chromosomal fusions, inversions, etc.
    STRUCTURAL = 6;

    // `CNV` indicates a variation in copy number.
    CNV = 7;
  }

  enum Effect {
    EFFECT_UNSPECIFIED = 0;

    // `EFFECT_OTHER` should be used when no other Effect
    // will suffice.
    EFFECT_OTHER = 1;

    // `FRAMESHIFT` indicates a mutation in which the insertion or
    // deletion of nucleotides resulted in a frameshift change.
    FRAMESHIFT = 2;

    // `FRAME_PRESERVING_INDEL` indicates a mutation in which a
    // multiple of three nucleotides has been inserted or deleted, resulting
    // in no change to the reading frame of the coding sequence.
    FRAME_PRESERVING_INDEL = 3;

    // `SYNONYMOUS_SNP` indicates a single nucleotide polymorphism
    // mutation that results in no amino acid change.
    SYNONYMOUS_SNP = 4;

    // `NONSYNONYMOUS_SNP` indicates a single nucleotide
    // polymorphism mutation that results in an amino acid change.
    NONSYNONYMOUS_SNP = 5;

    // `STOP_GAIN` indicates a mutation that leads to the creation
    // of a stop codon at the variant site. Frameshift mutations creating
    // downstream stop codons do not count as `STOP_GAIN`.
    STOP_GAIN = 6;

    // `STOP_LOSS` indicates a mutation that eliminates a
    // stop codon at the variant site.
    STOP_LOSS = 7;

    // `SPLICE_SITE_DISRUPTION` indicates that this variant is
    // found in a splice site for the associated transcript, and alters the
    // normal splicing pattern.
    SPLICE_SITE_DISRUPTION = 8;
  }

  enum ClinicalSignificance {
    CLINICAL_SIGNIFICANCE_UNSPECIFIED = 0;

    // `OTHER` should be used when no other clinical significance
    // value will suffice.
    CLINICAL_SIGNIFICANCE_OTHER = 1;

    UNCERTAIN = 2;

    BENIGN = 3;

    LIKELY_BENIGN = 4;

    LIKELY_PATHOGENIC = 5;

    PATHOGENIC = 6;

    DRUG_RESPONSE = 7;

    HISTOCOMPATIBILITY = 8;

    CONFERS_SENSITIVITY = 9;

    RISK_FACTOR = 10;

    ASSOCIATION = 11;

    PROTECTIVE = 12;

    // `MULTIPLE_REPORTED` should be used when multiple clinical
    // signficances are reported for a variant. The original clinical
    // significance values may be provided in the `info` field.
    MULTIPLE_REPORTED = 13;
  }

  // Type has been adapted from ClinVar's list of variant types.
  Type type = 1;

  // Effect of the variant on the coding sequence.
  Effect effect = 2;

  // The alternate allele for this variant. If multiple alternate alleles
  // exist at this location, create a separate variant for each one, as they
  // may represent distinct conditions.
  string alternate_bases = 3;

  // Google annotation ID of the gene affected by this variant. This should
  // be provided when the variant is created.
  string gene_id = 4;

  // Google annotation IDs of the transcripts affected by this variant. These
  // should be provided when the variant is created.
  repeated string transcript_ids = 5;

  // The set of conditions associated with this variant.
  // A condition describes the way a variant influences human health.
  repeated ClinicalCondition conditions = 6;

  // Describes the clinical significance of a variant.
  // It is adapted from the ClinVar controlled vocabulary for clinical
  // significance described at:
  // http://www.ncbi.nlm.nih.gov/clinvar/docs/clinsig/
  ClinicalSignificance clinical_significance = 7;
}

// A transcript represents the assertion that a particular region of the
// reference genome may be transcribed as RNA.
message Transcript {
  message Exon {
    // The start position of the exon on this annotation's reference sequence,
    // 0-based inclusive. Note that this is relative to the reference start, and
    // **not** the containing annotation start.
    int64 start = 1;

    // The end position of the exon on this annotation's reference sequence,
    // 0-based exclusive. Note that this is relative to the reference start, and
    // *not* the containing annotation start.
    int64 end = 2;

    // The frame of this exon. Contains a value of 0, 1, or 2, which indicates
    // the offset of the first coding base of the exon within the reading frame
    // of the coding DNA sequence, if any. This field is dependent on the
    // strandedness of this annotation (see
    // [Annotation.reverse_strand][google.genomics.v1.Annotation.reverse_strand]).
    // For forward stranded annotations, this offset is relative to the
    // [exon.start][google.genomics.v1.Transcript.Exon.start]. For reverse
    // strand annotations, this offset is relative to the
    // [exon.end][google.genomics.v1.Transcript.Exon.end] `- 1`.
    //
    // Unset if this exon does not intersect the coding sequence. Upon creation
    // of a transcript, the frame must be populated for all or none of the
    // coding exons.
    google.protobuf.Int32Value frame = 3;
  }

  message CodingSequence {
    // The start of the coding sequence on this annotation's reference sequence,
    // 0-based inclusive. Note that this position is relative to the reference
    // start, and *not* the containing annotation start.
    int64 start = 1;

    // The end of the coding sequence on this annotation's reference sequence,
    // 0-based exclusive. Note that this position is relative to the reference
    // start, and *not* the containing annotation start.
    int64 end = 2;
  }

  // The annotation ID of the gene from which this transcript is transcribed.
  string gene_id = 1;

  // The <a href="http://en.wikipedia.org/wiki/Exon">exons</a> that compose
  // this transcript. This field should be unset for genomes where transcript
  // splicing does not occur, for example prokaryotes.
  //
  // Introns are regions of the transcript that are not included in the
  // spliced RNA product. Though not explicitly modeled here, intron ranges can
  // be deduced; all regions of this transcript that are not exons are introns.
  //
  // Exonic sequences do not necessarily code for a translational product
  // (amino acids). Only the regions of exons bounded by the
  // [codingSequence][google.genomics.v1.Transcript.coding_sequence] correspond
  // to coding DNA sequence.
  //
  // Exons are ordered by start position and may not overlap.
  repeated Exon exons = 2;

  // The range of the coding sequence for this transcript, if any. To determine
  // the exact ranges of coding sequence, intersect this range with those of the
  // [exons][google.genomics.v1.Transcript.exons], if any. If there are any
  // [exons][google.genomics.v1.Transcript.exons], the
  // [codingSequence][google.genomics.v1.Transcript.coding_sequence] must start
  // and end within them.
  //
  // Note that in some cases, the reference genome will not exactly match the
  // observed mRNA transcript e.g. due to variance in the source genome from
  // reference. In these cases,
  // [exon.frame][google.genomics.v1.Transcript.Exon.frame] will not necessarily
  // match the expected reference reading frame and coding exon reference bases
  // cannot necessarily be concatenated to produce the original transcript mRNA.
  CodingSequence coding_sequence = 3;
}

message ExternalId {
  // The name of the source of this data.
  string source_name = 1;

  // The id used by the source of this data.
  string id = 2;
}

message CreateAnnotationSetRequest {
  // The annotation set to create.
  AnnotationSet annotation_set = 1;
}

message GetAnnotationSetRequest {
  // The ID of the annotation set to be retrieved.
  string annotation_set_id = 1;
}

message UpdateAnnotationSetRequest {
  // The ID of the annotation set to be updated.
  string annotation_set_id = 1;

  // The new annotation set.
  AnnotationSet annotation_set = 2;

  // An optional mask specifying which fields to update. Mutable fields are
  // [name][google.genomics.v1.AnnotationSet.name],
  // [source_uri][google.genomics.v1.AnnotationSet.source_uri], and
  // [info][google.genomics.v1.AnnotationSet.info]. If unspecified, all
  // mutable fields will be updated.
  google.protobuf.FieldMask update_mask = 3;
}

message DeleteAnnotationSetRequest {
  // The ID of the annotation set to be deleted.
  string annotation_set_id = 1;
}

message SearchAnnotationSetsRequest {
  // Required. The dataset IDs to search within. Caller must have `READ` access
  // to these datasets.
  repeated string dataset_ids = 1;

  // If specified, only annotation sets associated with the given reference set
  // are returned.
  string reference_set_id = 2;

  // Only return annotations sets for which a substring of the name matches this
  // string (case insensitive).
  string name = 3;

  // If specified, only annotation sets that have any of these types are
  // returned.
  repeated AnnotationType types = 4;

  // The continuation token, which is used to page through large result sets.
  // To get the next page of results, set this parameter to the value of
  // `nextPageToken` from the previous response.
  string page_token = 5;

  // The maximum number of results to return in a single page. If unspecified,
  // defaults to 128. The maximum value is 1024.
  int32 page_size = 6;
}

message SearchAnnotationSetsResponse {
  // The matching annotation sets.
  repeated AnnotationSet annotation_sets = 1;

  // The continuation token, which is used to page through large result sets.
  // Provide this value in a subsequent request to return the next page of
  // results. This field will be empty if there aren't any additional results.
  string next_page_token = 2;
}

message CreateAnnotationRequest {
  // The annotation to be created.
  Annotation annotation = 1;
}

message BatchCreateAnnotationsRequest {
  // The annotations to be created. At most 4096 can be specified in a single
  // request.
  repeated Annotation annotations = 1;

  // A unique request ID which enables the server to detect duplicated requests.
  // If provided, duplicated requests will result in the same response; if not
  // provided, duplicated requests may result in duplicated data. For a given
  // annotation set, callers should not reuse `request_id`s when writing
  // different batches of annotations - behavior in this case is undefined.
  // A common approach is to use a UUID. For batch jobs where worker crashes are
  // a possibility, consider using some unique variant of a worker or run ID.
  string request_id = 2;
}

message BatchCreateAnnotationsResponse {
  message Entry {
    // The creation status.
    google.rpc.Status status = 1;

    // The created annotation, if creation was successful.
    Annotation annotation = 2;
  }

  // The resulting per-annotation entries, ordered consistently with the
  // original request.
  repeated Entry entries = 1;
}

message GetAnnotationRequest {
  // The ID of the annotation to be retrieved.
  string annotation_id = 1;
}

message UpdateAnnotationRequest {
  // The ID of the annotation to be updated.
  string annotation_id = 1;

  // The new annotation.
  Annotation annotation = 2;

  // An optional mask specifying which fields to update. Mutable fields are
  // [name][google.genomics.v1.Annotation.name],
  // [variant][google.genomics.v1.Annotation.variant],
  // [transcript][google.genomics.v1.Annotation.transcript], and
  // [info][google.genomics.v1.Annotation.info]. If unspecified, all mutable
  // fields will be updated.
  google.protobuf.FieldMask update_mask = 3;
}

message DeleteAnnotationRequest {
  // The ID of the annotation to be deleted.
  string annotation_id = 1;
}

message SearchAnnotationsRequest {
  // Required. The annotation sets to search within. The caller must have
  // `READ` access to these annotation sets.
  // All queried annotation sets must have the same type.
  repeated string annotation_set_ids = 1;

  // Required. `reference_id` or `reference_name` must be set.
  oneof reference {
    // The ID of the reference to query.
    string reference_id = 2;

    // The name of the reference to query, within the reference set associated
    // with this query.
    string reference_name = 3;
  }

  // The start position of the range on the reference, 0-based inclusive. If
  // specified,
  // [referenceId][google.genomics.v1.SearchAnnotationsRequest.reference_id] or
  // [referenceName][google.genomics.v1.SearchAnnotationsRequest.reference_name]
  // must be specified. Defaults to 0.
  int64 start = 4;

  // The end position of the range on the reference, 0-based exclusive. If
  // [referenceId][google.genomics.v1.SearchAnnotationsRequest.reference_id] or
  // [referenceName][google.genomics.v1.SearchAnnotationsRequest.reference_name]
  // must be specified, Defaults to the length of the reference.
  int64 end = 5;

  // The continuation token, which is used to page through large result sets.
  // To get the next page of results, set this parameter to the value of
  // `nextPageToken` from the previous response.
  string page_token = 6;

  // The maximum number of results to return in a single page. If unspecified,
  // defaults to 256. The maximum value is 2048.
  int32 page_size = 7;
}

message SearchAnnotationsResponse {
  // The matching annotations.
  repeated Annotation annotations = 1;

  // The continuation token, which is used to page through large result sets.
  // Provide this value in a subsequent request to return the next page of
  // results. This field will be empty if there aren't any additional results.
  string next_page_token = 2;
}

// When an [Annotation][google.genomics.v1.Annotation] or
// [AnnotationSet][google.genomics.v1.AnnotationSet] is created, if `type` is
// not specified it will be set to `GENERIC`.
enum AnnotationType {
  ANNOTATION_TYPE_UNSPECIFIED = 0;

  // A `GENERIC` annotation type should be used when no other annotation
  // type will suffice. This represents an untyped annotation of the reference
  // genome.
  GENERIC = 1;

  // A `VARIANT` annotation type.
  VARIANT = 2;

  // A `GENE` annotation type represents the existence of a gene at the
  // associated reference coordinates. The start coordinate is typically the
  // gene's transcription start site and the end is typically the end of the
  // gene's last exon.
  GENE = 3;

  // A `TRANSCRIPT` annotation type represents the assertion that a
  // particular region of the reference genome may be transcribed as RNA.
  TRANSCRIPT = 4;
}