Terminology & Information Model

When biologists define terms in order to describe phenomena and observations, they rely on a background of human experience and intelligence for interpretation. Definitions may be abstract, perhaps correctly reflecting uncertainty of our understanding at the time. Unfortunately, such terms are not readily translatable into an unambiguous representation of knowledge.

For example, “allele” might refer to “an alternative form of a gene or locus” [Wikipedia], “one of two or more forms of the DNA sequence of a particular gene” [ISOGG], or “one of a set of coexisting sequence alleles of a gene” [Sequence Ontology]. Even for human interpretation, these definitions are inconsistent: does the definition precisely describe a specific change on a specific sequence, or, rather, a more general change on an undefined sequence? In addition, all three definitions are inconsistent with the practical need for a way to describe sequence changes outside regions associated with genes.

The computational representation of biological concepts requires translating precise biological definitions into data structures that can be used by implementers. This translation should result in a representation of information that is consistent with conventional biological understanding and, ideally, be able to accommodate future data as well. The resulting computational representation of information should also be cognizant of computational performance, the minimization of opportunities for misunderstanding, and ease of manipulating and transforming data.

Accordingly, for each term we define below, we begin by describing the term as used by biologists (biological definition) as available. When a term has multiple biological definitions, we explicitly choose one of them for the purposes of this specification. We then provide a computer modelling definition (computational definition) that reformulates the biological definition in terms of information content. We then translate each of these computational definitions into precise specifications for the (logical model). Terms are ordered “bottom-up” so that definitions depend only on previously-defined terms.

Note

The keywords “MUST”, “MUST NOT”, “REQUIRED”, “SHALL”, “SHALL NOT”, “SHOULD”, “SHOULD NOT”, “RECOMMENDED”, “MAY”, and “OPTIONAL” in this document are to be interpreted as described in RFC 2119.

Data Model Notes and Principles

  • VRS uses snake_case to represent compound words. Although the schema is currently JSON-based (which would typically use camelCase), VRS itself is intended to be neutral with respect to languages and database.
  • VRS objects are value objects. Two objects are considered equal if and only if their respective attributes are equal. As value objects, VRS objects are used as primitive types and SHOULD NOT be used as containers for related data. Instead, related data should be associated with VRS objects through identifiers. See Computed Identifiers.
  • Error handling is intentionally unspecified and delegated to implementation. VRS provides foundational data types that enable significant flexibility. Except where required by this specification, implementations may choose whether and how to validate data. For example, implementations MAY choose to validate that particular combinations of objects are compatible, but such validation is not required.
  • We recognize that a common desire may be to have human-readable identifiers associated with VRS objects. We recommend using the _id field (see Optional Attributes below) to create a lookup for any such identifiers (see example usage), and provide reference methods for creating VRS identifiers from other common variant formats (see the HGVS translation example).

Optional Attributes

  • VRS attributes use a leading underscore to represent optional attributes that are not part of the value object. Such attributes are not considered when evaluating equality or creating computed identifiers. Currently, the only such attribute in the specification is the _id attribute.
  • The _id attribute is available to identifiable objects, and MAY be used by an implementation to store the identifier for a VRS object. If used, the stored _id element MUST be a CURIE. If used for creating a Truncated Digest (sha512t24u) for parent objects, the stored element must be a GA4GH Computed Identifier.

Primitive Concepts

CURIE

Biological Definition

None.

Computational Definition

A CURIE formatted string. A CURIE string has the structure prefix:reference (W3C Terminology).

Implementation Guidance

  • All identifiers in VRS MUST be a valid Compact URI (CURIE), regardless of whether the identifier refers to GA4GH VRS objects or external data.
  • For GA4GH VRS objects, this specification RECOMMENDS using globally unique Computed Identifiers for use within and between systems.
  • For external data, CURIE-formatted identifiers MUST be used. When an appropriate namespace exists at identifiers.org, that namespace MUST be used. When an appropriate namespace does not exist at identifiers.org, support is implementation-dependent. That is, implementations MAY choose whether and how to support informal or local namespaces.
  • Implementations MUST use CURIE identifiers verbatim. Implementations MAY NOT modify CURIEs in any way (e.g., case-folding).

Examples

Identifiers for GRCh38 chromosome 19:

ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl
refseq:NC_000019.10
grch38:19

See Identifier Construction for examples of CURIE-based identifiers for VRS objects.

Residue

Biological Definition

A residue refers to a specific monomer within the polymeric chain of a protein or nucleic acid (Source: Wikipedia Residue page).

Computational Definition

A character representing a specific residue (i.e., molecular species) or groupings of these (“ambiguity codes”), using one-letter IUPAC abbreviations for nucleic acids and amino acids.

Sequence

Biological Definition

A contiguous, linear polymer of nucleic acid or amino acid residues.

Computational Definition

A character string of Residues that represents a biological sequence using the conventional sequence order (5’-to-3’ for nucleic acid sequences, and amino-to-carboxyl for amino acid sequences). IUPAC ambiguity codes are permitted in Sequences.

Information Model

A Sequence is a string, constrained to contain only characters representing IUPAC nucleic acid or amino acid codes.

Implementation Guidance

  • Sequences MAY be empty (zero-length) strings. Empty sequences are used as the replacement Sequence for deletion Alleles.
  • Sequences MUST consist of only uppercase IUPAC abbreviations, including ambiguity codes.
  • A Sequence provides a stable coordinate system by which an Allele MAY be located and interpreted.
  • A Sequence MAY have several roles. A “reference sequence” is any Sequence used to define an Allele. A Sequence that replaces another Sequence is called a “replacement sequence”.
  • In some contexts outside VRS, “reference sequence” may refer to a member of set of sequences that comprise a genome assembly. In the VRS specification, any sequence may be a “reference sequence”, including those in a genome assembly.
  • For the purposes of representing sequence variation, it is not necessary that Sequences be explicitly “typed” (i.e., DNA, RNA, or AA).

Non-variation classes

SequenceInterval (Abstract Class)

Biological Definition

None.

Computational Definition

The SequenceInterval abstract class defines a range on a Sequence, possibly with length zero, and specified using Interbase Coordinates. An Interval MAY be a SimpleInterval with a single start and end coordinate. Future Location and SequenceInterval types will enable other methods for describing where Variation occurs. Any of these MAY be used as the SequenceInterval for Location.

SimpleInterval

Computational Definition

A SequenceInterval (Abstract Class) with a single start and end coordinate.

Information Model

Field Type Limits Description
type string 1..1 MUST be “SimpleInterval”
start uint64 1..1 start position
end uint64 1..1 end position

Implementation Guidance

  • Implementations MUST enforce values 0 ≤ start ≤ end. In the case of double-stranded DNA, this constraint holds even when a feature is on the complementary strand.

  • VRS uses Interbase coordinates because they provide conceptual consistency that is not possible with residue-based systems (see rationale). Implementations will need to convert between interbase and 1-based inclusive residue coordinates familiar to most human users.

  • Interbase coordinates start at 0 (zero).

  • The length of an interval is end - start.

  • An interval in which start == end is a zero width point between two residues.

  • An interval of length == 1 MAY be colloquially referred to as a position.

  • Two intervals are equal if the their start and end coordinates are equal.

  • Two intervals intersect if the start or end coordinate of one is strictly between the start and end coordinates of the other. That is, if:

    • b.start < a.start < b.end OR
    • b.start < a.end < b.end OR
    • a.start < b.start < a.end OR
    • a.start < b.end < a.end
  • Two intervals a and b coincide if they intersect or if they are equal (the equality condition is REQUIRED to handle the case of two identical zero-width SimpleIntervals).

  • <start, end>=<0,0> refers to the point with width zero before the first residue.

  • <start, end>=<i,i+1> refers to the i+1th (1-based) residue.

  • <start, end>=<N,N> refers to the position after the last residue for Sequence of length N.

  • See example notebooks in GA4GH VRS Python Implementation.

Examples

{
  "end": 44908822,
  "start": 44908821,
  "type": "SimpleInterval"
}

CytobandInterval

Computational Definition

A contiguous region specified by chromosomal bands features.

Information Model

Field Type Limits Description
type string 1..1 MUST be “CytobandInterval”
start string 1..1 name of feature start
end string 1..1 name of feature end

Implementation Guidance

  • start and end attributes of CytobandInterval are intentionally specified vaguely in order to accommodate a wide variety of uses. Examples include named markers on chromosomes, cytogenetic bands, and legacy marker names found in older scientific literature.
  • When CytobandInterval refers to cytogentic bands, the valid values for, and the syntactic structure of, the start and end depend on the species. When using CytobandInterval to refer to human cytogentic bands, ISCN conventions MUST be used. Bands are denoted by the arm (“p” or “q”) and position (e.g., “22”, “22.3”, or the symbolic values “cen”, “tel”, or “ter”). If start and end are on different arms, they SHOULD correspond to the p-arm and q-arm locations respectively. If start and end are on the same arm, start MUST be the more centromeric position (i.e., with lower band and sub-band numbers).

Examples

{
  "end": "q22.3",
  "start": "q22.2",
  "type": "CytobandInterval"
}

Location (Abstract Class)

Biological Definition

As used by biologists, the precision of “location” (or “locus”) varies widely, ranging from precise start and end numerical coordinates defining a Location, to bounded regions of a sequence, to conceptual references to named genomic features (e.g., chromosomal bands, genes, exons) as proxies for the Locations on an implied reference sequence.

Computational Definition

The Location abstract class refers to position of a contiguous segment of a biological sequence. The most common and concrete Location is a SequenceLocation, i.e., a Location based on a named sequence and an Interval on that sequence. Additional Intervals and Locations may also be conceptual or symbolic locations, such as a cytoband region or a gene. Any of these may be used as the Location for Variation.

Implementation Guidance

  • Location refers to a position. Although it MAY imply a sequence, the two concepts are not interchangeable, especially when the location is non-specific (e.g., a range) or symbolic (a gene).

ChromosomeLocation

Biological Definition

Chromosomal locations based on named features.

Computational Definition

A ChromosomeLocation is a Location (Abstract Class) that is defined by a named chromosomal features.

Information Model

Field Type Limits Description
_id CURIE 0..1 Location id; MUST be unique within document
type string 1..1 MUST be “ChromosomeLocation”
species CURIE 1..1 An external reference to a species taxonomy. Default: “taxonomy:9606” (Human). See Implementation Guidance, below.
chr string 1..1 The symbolic chromosome name
interval CytobandInterval 1..1 The chromosome region based on feature names

Implementation Guidance

  • ChromosomeLocation is intended to enable the representation of cytogenetic results from karyotyping or low-resolution molecular methods, particularly those found in older scientific literature. Precise SequenceLocation should be preferred when nucleotide-scale location is known.
  • species is specified using the NCBI taxonomy. The CURIE prefix MUST be “taxonomy”, corresponding to the NCBI taxonomy prefix at identifiers.org, and the CURIE reference MUST be an NCBI taxonomy identifier (e.g., 9606 for Homo sapiens).
  • ChromosomeLocation is intended primarily for Humans. Support for other species is possible and will be considered based on community feedback.
  • chromosome is an archetypal chromosome name. Valid values for, and the syntactic structure of, chromosome depends on the species. chromosome MUST be an official sequence name from NCBI Assembly. For Humans, valid chromosome names are 1..22, X, Y (case-sensitive).
  • interval refers to a contiguous region specified named markers, which are presumed to exist on the specified chromosome. See CytobandInterval for additional information.
  • The conversion of ChromosomeLocation instances to SequenceLocation instances is out-of-scope for VRS. When converting start and end to SequenceLocations, the positions MUST be interpreted as inclusive ranges that cover the maximal extent of the region.
  • Data for converting cytogenetic bands to precise sequence coordinates are available at NCBI GDP, UCSC GRCh37 (hg19), UCSC GRCh38 (hg38), and bioutils (Python).
  • See also the rationale for Not using External Chromosome Declarations.

Examples

{
  "chr": "11",
  "interval": {
    "end": "q22.3",
    "start": "q22.2",
    "type": "CytobandInterval"
    },
  "species_id": "taxonomy:9606",
  "type": "ChromosomeLocation"
}

SequenceLocation

Biological Definition

A specified subsequence within another sequence that is used as a reference sequence.

Computational Definition

A Location subclass for describing a defined SequenceInterval (Abstract Class) on a named Sequence.

Information Model

Field Type Limits Description
_id CURIE 0..1 Location id; MUST be unique within document
type string 1..1 MUST be “SequenceLocation”
sequence_id CURIE 1..1 An id mapping to the Computed Identifiers of the external database Sequence containing the sequence to be located.
interval SequenceInterval (Abstract Class) 1..1 Position of feature on reference sequence specified by sequence_id.

Implementation Guidance

  • For a Sequence of length n:
    • 0 ≤ interval.startinterval.endn
    • interbase coordinate 0 refers to the point before the start of the Sequence
    • interbase coordinate n refers to the point after the end of the Sequence.
  • Coordinates MUST refer to a valid Sequence. VRS does not support referring to intronic positions within a transcript sequence, extrapolations beyond the ends of sequences, or other implied sequence.

Important

HGVS permits variants that refer to non-existent sequence. Examples include coordinates extrapolated beyond the bounds of a transcript and intronic sequence. Such variants are not representable using VRS and MUST be projected to a genomic reference in order to be represented.

Examples

{
  "interval": {
    "end": 44908822,
    "start": 44908821,
    "type": "SimpleInterval"
  },
  "sequence_id": "ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
  "type": "SequenceLocation"
}

State (Abstract Class)

Biological Definition

None.

Computational Definition

State objects are one of two primary components specifying a VRS Allele (in addition to Location (Abstract Class)), and the designated components for representing change (or non-change) of the features indicated by the Allele Location. As an abstract class, State currently encompasses single and contiguous Sequence changes (see SequenceState), with additional types under consideration (see State Classes).

SequenceState

Biological Definition

None.

Computational Definition

The SequenceState class specifically captures a Sequence as a State (Abstract Class). This is the State class to use for representing “ref-alt” style variation, including SNVs, MNVs, del, ins, and delins.

Information Model

Field Type Limits Description
type string 1..1 MUST be “SequenceState”
sequence string 1..1 The string of sequence residues that is to be used as the state for other types.

Examples

{
  "sequence": "T",
  "type": "SequenceState"
}

Variation

The Variation class is the conceptual root of all types of variation, both current and future.

Biological Definition

In biology, variation is often used to mean sequence variation, describing the differences observed in DNA or AA bases among individuals.

Computational Definition

The Variation abstract class is the top-level object in the Current Variation Representation Specfication Schema and represents the concept of a molecular state. The representation and types of molecular states are widely varied, and there are several Variation Classes currently under consideration to capture this diversity. The primary Variation subclass defined by the VRS HEAD specification is the Allele, with the Text subclass for capturing other Variations that are not yet covered.

Allele

Biological Definition

One of a number of alternative forms of the same gene or same genetic locus. In the context of biological sequences, “allele” refers to one of a set of specific changes within a Sequence. In the context of VRS, Allele refers to a Sequence or Sequence change with respect to a reference sequence, without regard to genes or other features.

Computational Definition

An Allele is an assertion of the State of a biological sequence at a Location.

Information Model

Field Type Limits Description
_id CURIE 0..1 Variation Id; MUST be unique within document
type string 1..1 MUST be “Allele”
location Location (Abstract Class) | CURIE 1..1 Where Allele is located
state State (Abstract Class) 1..1 State at location

Implementation Guidance

  • The State and Location subclasses respectively represent diverse kinds of sequence changes and mechanisms for describing the locations of those changes, including varying levels of precision of sequence location and categories of sequence changes.

  • Implementations MUST enforce values interval.end ≤ sequence_length when the Sequence length is known.

  • Alleles are equal only if the component fields are equal: at the same location and with the same state.

  • Alleles MAY have multiple related representations on the same Sequence type due to normalization differences.

  • Implementations SHOULD normalize Alleles using “justified” normalization whenever possible to facilitate comparisons of variation in regions of representational ambiguity.

  • Implementations MUST normalize Alleles using “justified” normalization when generating a Computed Identifiers.

  • When the alternate Sequence is the same length as the interval, the lengths of the reference Sequence and imputed Sequence are the same. (Here, imputed sequence means the sequence derived by applying the Allele to the reference sequence.) When the replacement Sequence is shorter than the length of the interval, the imputed Sequence is shorter than the reference Sequence, and conversely for replacements that are larger than the interval.

  • When the replacement is “” (the empty string), the Allele refers to a deletion at this location.

  • The Allele entity is based on Sequence and is intended to be used for intragenic and extragenic variation. Alleles are not explicitly associated with genes or other features.

  • Biologically, referring to Alleles is typically meaningful only in the context of empirical alternatives. For modelling purposes, Alleles MAY exist as a result of biological observation or computational simulation, i.e., virtual Alleles.

  • “Single, contiguous” refers the representation of the Allele, not the biological mechanism by which it was created. For instance, two non-adjacent single residue Alleles could be represented by a single contiguous multi-residue Allele.

  • The terms “allele” and “variant” are often used interchangeably, although this use may mask subtle distinctions made by some users.

    • In the genetics community, “allele” may also refer to a haplotype.
    • “Allele” connotes a state whereas “variant” connotes a change between states. This distinction makes it awkward to use variant to refer to the concept of an unchanged position in a Sequence and was one of the factors that influenced the preference of “Allele” over “Variant” as the primary subject of annotations.
    • See Use “Allele” rather than “Variant” for further details.
  • When a trait has a known genetic basis, it is typically represented computationally as an association with an Allele.

  • This specification’s definition of Allele applies to all Sequence types (DNA, RNA, AA).

Examples

{
   "location": {
      "interval": {
         "end": 44908822,
         "start": 44908821,
         "type": "SimpleInterval"
      },
      "sequence_id": "ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
      "type": "SequenceLocation"
   },
   "state": {
      "sequence": "T",
      "type": "SequenceState"
   },
   "type": "Allele"
}

Text

Biological Definition

None

Computational Definition

The Text subclass of Variation is intended to capture textual descriptions of variation that cannot be parsed by other Variation subclasses, but are still treated as variation.

Information Model

Field Type Limits Description
_id CURIE 0..1 Variation Id; MUST be unique within document
type string 1..1 MUST be “Text”
definition string 1..1 The textual variation representation not parsable by other subclasses of Variation.

Implementation Guidance

  • An implementation MUST represent Variation with subclasses other than Text if possible.
  • An implementation SHOULD define or adopt conventions for defining the strings stored in Text.definition.
  • If a future version of VRS is adopted by an implementation and the new version enables defining existing Text objects under a different Variation subclass, the implementation MUST construct a new object under the other Variation subclass. In such a case, an implementation SHOULD persist the original Text object and respond to queries matching the Text object with the new object.
  • Additional Variation subclasses are continually under consideration. Please open a GitHub issue if you would like to propose a Variation subclass to cover a needed variation representation.

Examples

{
  "definition": "APOE loss",
  "type": "Text"
}

Haplotype

Biological Definition

A specific combination of Alleles that occur together on single sequence in one or more individuals.

Computational Definition

A specific combination of non-overlapping Alleles that co-occur on the same reference sequence.

Information Model

Field Type Limits Description
_id CURIE 0..1 Variation Id; MUST be unique within document
type string 1..1 MUST be “Haplotype”
members Allele[] | CURIE[] 1..* List of Alleles, or references to Alleles, that comprise this Haplotype

Implementation Guidance

  • Haplotypes are an assertion of Alleles known to occur “in cis” or “in phase” with each other.
  • All Alleles in a Haplotype MUST be defined on the same reference sequence.
  • Alleles within a Haplotype MUST not overlap (“overlap” is defined in Interval).
  • The locations of Alleles within the Haplotype MUST be interpreted independently. Alleles that create a net insertion or deletion of sequence MUST NOT change the location of “downstream” Alleles.
  • The members attribute is required and MUST contain at least one Allele.

Sources

  • ISOGG: Haplotype — A haplotype is a combination of alleles (DNA sequences) at different places (loci) on the chromosome that are transmitted together. A haplotype may be one locus, several loci, or an entire chromosome depending on the number of recombination events that have occurred between a given set of loci.
  • SO: haplotype (SO:0001024) — A haplotype is one of a set of coexisting sequence variants of a haplotype block.
  • GENO: Haplotype (GENO:0000871) - A set of two or more sequence alterations on the same chromosomal strand that tend to be transmitted together.

Examples

An APOE-ε1 Haplotype with inline Alleles:

{
  "members": [
    {
      "location": {
        "interval": {
          "end": 44908684,
          "start": 44908683,
          "type": "SimpleInterval"
        },
        "sequence_id": "ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
        "type": "SequenceLocation"
      },
      "state": {
        "sequence": "C",
        "type": "SequenceState"
      },
      "type": "Allele"
    },
    {
      "location": {
        "interval": {
          "end": 44908822,
          "start": 44908821,
          "type": "SimpleInterval"
        },
        "sequence_id": "ga4gh:SQ.IIB53T8CNeJJdUqzn9V_JnRtQadwWCbl",
        "type": "SequenceLocation"
      },
      "state": {
        "sequence": "T",
        "type": "SequenceState"
      },
      "type": "Allele"
    }
  ],
  "type": "Haplotype"
}

The same APOE-ε1 Haplotype with referenced Alleles:

{
  "members": [
    "ga4gh:VA.iXjilHZiyCEoD3wVMPMXG3B8BtYfL88H",
    "ga4gh:VA.EgHPXXhULTwoP4-ACfs-YCXaeUQJBjH_"
  ],
  "type": "Haplotype"
}

The GA4GH computed identifier for these Haplotypes is ga4gh:VH.NAVnEuaP9gf41OxnPM56XxWQfdFNcUxJ, regardless of the whether the Variation objects are inlined or referenced, and regardless of order. See Computed Identifiers for more information.

VariationSet

Biological Definition

Sets of variation are used widely, such as sets of variants in dbSNP or ClinVar that might be related by function.

Computational Definition

An unconstrained set of Variation objects or references.

Information Model

Field Type Limits Description
_id CURIE 0..1 Identifier of the VariationSet.
type string 1..1 MUST be “VariationSet”
members Variation[] or CURIE[] 0..* List of Variation objects or identifiers. Attribute is required, but MAY be empty.

Implementation Guidance

  • The VariationSet identifier MAY be computed as described in Computed Identifiers, in which case the identifier effectively refers to a static set because a different set of members would generate a different identifier.
  • members may be specified as Variation objects or CURIE identifiers.
  • CURIEs MAY refer to entities outside the ga4gh namespace. However, objects that use non-ga4gh identifiers MAY NOT use the Computed Identifiers mechanism.
  • VariationSet identifiers computed using the GA4GH Computed Identifiers process do not depend on whether the Variation objects are inlined or referenced, and do not depend on the order of members.
  • Elements of members must be subclasses of Variation, which permits sets to be nested.
  • Recursive sets are not meaningful and are not supported.
  • VariationSets may be empty.

Examples

Inlined Variation objects:

{
  "members": [
    {
      "location": {
        "interval": {
          "end": 11,
          "start": 10,
          "type": "SimpleInterval"
        },
        "sequence_id": "ga4gh:SQ.01234abcde",
        "type": "SequenceLocation"
      },
      "state": {
        "sequence": "C",
        "type": "SequenceState"
      },
      "type": "Allele"
    },
    {
      "location": {
        "interval": {
          "end": 21,
          "start": 20,
          "type": "SimpleInterval"
        },
        "sequence_id": "ga4gh:SQ.01234abcde",
        "type": "SequenceLocation"
      },
      "state": {
        "sequence": "C",
        "type": "SequenceState"
      },
      "type": "Allele"
    },
    {
      "location": {
        "interval": {
          "end": 31,
          "start": 30,
          "type": "SimpleInterval"
        },
        "sequence_id": "ga4gh:SQ.01234abcde",
        "type": "SequenceLocation"
      },
      "state": {
        "sequence": "C",
        "type": "SequenceState"
      },
      "type": "Allele"
    }
  ],
  "type": "VariationSet"
}

Referenced Variation objects:

{
  "members": [
    "ga4gh:VA.6xjH0Ikz88s7MhcyN5GJTa1p712-M10W",
    "ga4gh:VA.7k2lyIsIsoBgRFPlfnIOeCeEgj_2BO7F",
    "ga4gh:VA.ikcK330gH3bYO2sw9QcTsoptTFnk_Xjh"
  ],
  "type": "VariationSet"
}

The GA4GH computed identifier for these sets is ga4gh:VS.WVC_R7OJ688EQX3NrgpJfsf_ctQUsVP3, regardless of the whether the Variation objects are inlined or referenced, and regardless of order. See Computed Identifiers for more information.