ISO/IEC 23092-1:2019

INTERNATIONAL ISO/IEC
STANDARD 23092-1
First edition
2019-07
Information technology — Genomic
information representation —
Part 1:
Transport and storage of genomic
information
Technologie de l'information — Représentation des informations
génomiques —
Partie 1: Transport et stockage des informations génomiques
Reference number
ISO/IEC 23092-1:2019(E)
©
ISO/IEC 2019

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ISO/IEC 23092-1:2019(E)

COPYRIGHT PROTECTED DOCUMENT
© ISO/IEC 2019
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
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Published in Switzerland
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ISO/IEC 23092-1:2019(E)

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Mathematical operators . 4
4.1 Arithmetic operators . 4
4.2 Logical operators . 4
4.3 Relational operators . 4
4.4 Bitwise operators. 5
4.5 Assignment . 5
4.6 Unary operators . 5
5 Structure of coded genomic data . 5
5.1 Genomic records . 5
5.2 Data classes . 6
5.3 Access units . 6
5.4 Datasets . 7
5.5 Selective access . 7
6 Data format . 7
6.1 Format structure . 7
6.1.1 General. 7
6.1.2 Box order . 9
6.2 Syntax and semantics .10
6.2.1 Method of specifying syntax in tabular form .10
6.2.2 Bit ordering .11
6.2.3 Specification of syntax functions .11
6.3 Syntax for representation .11
6.4 Output data unit .12
6.5 Data structures common to file format and transport format .13
6.5.1 Dataset group.13
6.5.2 Dataset .20
6.5.3 Access unit .27
6.5.4 Block .31
6.6 Data structures specific to file format .32
6.6.1 General.32
6.6.2 File header .32
6.6.3 Indexing .33
6.6.4 Descriptor stream .38
6.6.5 Offset .40
6.7 Data structures specific to transport format .41
6.7.1 General.41
6.7.2 Data streams .41
6.7.3 Dataset mapping table list .41
6.7.4 Dataset mapping table .42
6.7.5 Packet .43
6.8 Reference procedure to convert transport format to file format .44
Annex A (informative) IETF – RFC 3986 specification summary .47
Annex B (informative) Selective access strategies .48
Annex C (informative) Depacketization process .51
Bibliography .53
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Foreword
ISO (the International Organization for Standardization) and IEC (the International Electrotechnical
Commission) form the specialized system for worldwide standardization. National bodies that
are members of ISO or IEC participate in the development of International Standards through
technical committees established by the respective organization to deal with particular fields of
technical activity. ISO and IEC technical committees collaborate in fields of mutual interest. Other
international organizations, governmental and non-governmental, in liaison with ISO and IEC, also
take part in the work.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for
the different types of document should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject
of patent rights. ISO and IEC shall not be held responsible for identifying any or all such patent
rights. Details of any patent rights identified during the development of the document will be in the
Introduction and/or on the ISO list of patent declarations received (see www .iso .org/patents) or the IEC
list of patent declarations received (see http: //patents .iec .ch).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see www .iso
.org/iso/foreword .html.
This document was prepared by Joint Technical Committee ISO/IEC JTC 1, Information technology,
Subcommittee SC 29, Coding of audio, picture, multimedia and hypermedia information.
A list of all parts in the ISO/IEC 23092 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/members .html.
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ISO/IEC 23092-1:2019(E)

Introduction
The advent of high-throughput sequencing (HTS) technologies has the potential to boost the adoption
of genomic information in everyday practice, ranging from biological research to personalized genomic
medicine in clinics. As a consequence, the volume of generated data has increased dramatically during
the last few years, and an even more pronounced growth is expected in the near future.
At the moment, genomic information is mostly exchanged through a variety of data formats, such as
FASTA/FASTQ for unaligned sequencing reads and SAM/BAM/CRAM for aligned reads. With respect to
such formats, the ISO/IEC 23092 series provides a new solution for the representation and compression
of genome sequencing information by:
— Specifying an abstract representation of the sequencing data rather than a specific format with its
direct implementation.
— Being designed at a time point when technologies and use cases are more mature. This permits the
addressing of one limitation of the textual SAM format, for which incremental ad-hoc addition of
features followed along the years, resulting in an overall redundant and suboptimal format which
at the same time results not general and unnecessarily complicated.
— Normatively separating free-field user-defined information with no clear semantics from the
normative genomic data representation. This allows a fully interoperable and automatic exchange
of information between different data producers.
— Allowing multiplexing of relevant metadata information with the data since data and metadata are
partitioned at different conceptual levels.
— Following a strict and supervised development process which has proven successful in the last
30 years in the domain of digital media for the transport format, the file format, the compressed
representation and the application program interfaces.
This document provides the enabling technology that will allow the community to create an ecosystem
of novel, interoperable, solutions in the field of genomic information processing. In particular, it offers:
— Consistent, general and properly designed format definitions and data structures to store sequencing
and alignment information. A robust framework which can be used as a foundation to implement
different compression algorithms.
— Speed and flexibility in the selective access to coded data, by means of newly-designed data
clustering and optimized storage methodologies.
— Low latency in data transmission and consequent fast availability at remote locations, based on
transmission protocols inspired by real-time application domains.
— Built-in privacy and protection of sensitive information, thanks to a flexible framework which
allows customizable, secured access at all layers of the data hierarchy.
— Reliability of the technology and interoperability among tools and systems, owing to the provision
of a normative procedure to assess conformance to this document on an exhaustive dataset.
— Support to the implementation of a complete ecosystem of compliant devices and applications,
through the availability of a normative reference implementation covering the totality of the
ISO/IEC 23092 series.
The fundamental structure of the ISO/IEC 23092 series data representation is the genomic record. The
genomic record is a data structure consisting of either a single sequence read, or a paired sequence
read, and its associated sequencing and alignment information; it may contain detailed mapping and
alignment data, a single or paired read identifier (read name) and quality values.
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Without breaking traditional approaches, the genomic record introduced in the ISO/IEC 23092 series
provides a more compact, simpler and manageable data structure grouping all the information related
to a single DNA template, from simple sequencing data to sophisticated alignment information.
The genomic record, although it is an appropriate logic data structure for interaction and manipulation of
coded information, is not a suitable atomic data structure for compression. To achieve high compression
ratios, it is necessary to group genomic records into clusters and to transform the information of the
same type into sets of descriptors structured into homogeneous blocks. Furthermore, when dealing
with selective data access, the genomic record is a too small unit to allow effective and fast information
retrieval.
For these reasons, this document introduces the concept of access unit, which is the fundamental
structure for coding and access to information in the compressed domain.
The access unit is the smallest data structure that can be decoded by a decoder compliant with
ISO/IEC 23092-2. An access unit is composed of one block for each descriptor used to represent the
information of its genomic records; therefore, a block payload is the coded representation of all the data
of the same type (i.e. a descriptor) in a cluster.
In addition to clusters of genomic records compressed into access units, reads are further classified in
six data classes: five classes are defined according to the result of their alignment against one or more
reference sequences; the sixth class contains either reads that could not be mapped or raw sequencing
data. The classification of sequence reads into classes enables the development of powerful selective
data access. In fact, access units inherit a specific data characterization (e.g. perfect matches in Class
P, substitutions in Class M, indels in Class I, half-mapped reads in Class HM) from the genomic records
composing them, and thus constitute a data structure capable of providing powerful filtering capability
for the efficient support of many different use cases.
Access units are the fundamental, finest grain data structure in terms of content protection and in
terms of metadata association. In other words, each access unit can be protected individually and
independently. Figure 1 shows how access units, blocks and genomic records relate to each other in the
ISO/IEC 23092 series data structure.
Figure 1 — Access units, blocks and genomic records
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Figure 2 — High-level data structure: datasets and dataset group
A dataset is a coded data structure containing headers and one or more access units. Typical datasets
could, for example, contain the complete sequencing of an individual, or a portion of it. Other datasets
could contain, for example, a reference genome or a subset of its chromosomes. Datasets are grouped in
dataset groups, as shown in Figure 2.
A simplified diagram of the dataset decoding process is shown in Figure 3.
Figure 3 — Decoding process
This document defines the syntax and semantics of the data formats for both transport and storage of
genomic information. According to this document, the compressed sequencing data can be multiplexed
into a normative bitstream suitable for packetization for real-time transport over typical network
protocols. In storage use cases, coded data can be encapsulated into a file format with the possibility
to organize blocks per descriptor stream or per access units, to further optimize the selective access
performance to the type of data access required by the different application scenarios. This document
further provides a reference process to convert a normative transport stream into a normative file
format and vice versa.
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The International Organization for Standardization (ISO) and International Electrotechnical
Commission (IEC) draw attention to the fact that it is claimed that compliance with this document may
involve the use of a patent.
ISO and IEC take no position concerning the evidence, validity and scope of this patent right. The
holder of this patent right has assured ISO and IEC that he/she is willing to negotiate licences under
reasonable and non-discriminatory terms and conditions with applicants throughout the world. In this
respect, the statement of the holder of this patent right is registered with ISO and IEC. Information may
be obtained from:
GenomSys SA
EPFL Innovation Park Building C
CH-1015 Lausanne
Switzerland
info@genomsys .com
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights other than those identified above. ISO and IEC shall not be held responsible for identifying
any or all such patent rights.
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INTERNATIONAL STANDARD ISO/IEC 23092-1:2019(E)
Information technology — Genomic information
representation —
Part 1:
Transport and storage of genomic information
1 Scope
This document specifies data formats for both transport and storage of genomic information, including
the conversion process.
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO/IEC 10646, Universal Coded Character Set (UCS)
1)
ISO/IEC FDIS 23092-2:2019 , Information technology — Genomic information representation — Part 2:
Coding of genomic information
2)
ISO/IEC FDIS 23092-3 , Information technology — Genomic information representation — Part 3:
Metadata and application programming interfaces (APIs)
IETF RFC 3986, Uniform Resource Identifier (URI): Generic Syntax
IETF RFC 7320, URI Design and Ownership
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https: //www .iso .org/obp
— IEC Electropedia: available at http: //www .electropedia .org/
3.1
access unit
logical data structure containing a coded representation of genomic information to facilitate bit stream
access and manipulation
3.2
access unit covered region
genomic range comprised between the access unit start position and the access unit end position,
inclusive
1) Under preparation. Stage at time of publication: ISO/IEC FDIS 23092-2:2019.
2) Under preparation. Stage at time of publication: ISO/IEC FDIS 23092-3:2019.
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3.3
access unit start position
position of the left-most mapped base among the first alignments of all genomic records contained in
the access unit, irrespective of the strand
3.4
access unit end position
position of the right-most mapped base among the first alignments of all genomic records contained in
the access unit, irrespective of the strand
3.5
access unit range
genomic range comprised between the access unit start position and the right-most genomic record
position among all genomic records contained in the access unit
3.6
access unit covered region
genomic range comprised between the access unit start position and the access unit end position
inclusive
3.7
alignment
information describing the similarity between a sequence (typically a sequencing read) and a reference
sequence (for instance, a reference genome)
3.8
box
object-oriented building unit defined by a unique type identifier and length
3.9
cluster
aggregation of genomic records
3.10
cluster signature
signature
sequence of nucleotides that is common to most or all genomic records belonging to a cluster
3.11
container box
box (3.8) whose sole purpose is to contain and group a set of related boxes
3.12
data stream
set of packets (3.20) transporting the same data type
3.13
extended access unit start position
position of the left-most mapped base among all alignments of all genomic records contained in the
access unit, irrespective of the strand
3.14
extended access unit end position
position of the right-most mapped base among all alignments of all genomic records contained in the
access unit, irrespective of the strand
3.15
file format
set of data structures for the storage of coded information
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3.16
genomic position
position
integer number representing the zero-based position of a nucleotide within a reference sequence
3.17
genomic region
region
genomic interval between a start nucleotide position and an end nucleotide position, inclusive
3.18
genomic range
range
interval of positions on a reference sequence defined by a start position s and an end position e such
that s ≤ e; the start and the end positions of a genomic range are always included in the range
3.19
mapped base
base of the aligned read that either matches the corresponding base on the reference sequence or can
be turned into the corresponding base on the reference sequence via a substitution
3.20
packet
transmission unit transporting segments of any of the data structures defined in this document
3.21
reference genome
representative example of the sequences for a species’ genetic material
Note 1 to entry: Genetic material meaning the sequences of the DNA molecules present in a typical cell of that
species.
3.22
reference sequence
nucleic acid sequence with biological relevance
Note 1 to entry: Each reference sequence is indexed by a one-dimensional integer coordinate system whereby
each integer within range identifies a single nucleotide. Coordinate values can only be equal to or larger than
zero. The coordinate system in the context of this standard is zero-based (i.e. the first nucleotide has coordinate 0
and it is said to be at position 0) and linearly increasing within the string from left to right.
3.23
genomic segment
segment
contiguous sequence of nucleotides, typically output of the sequencing process and sequenced from one
strand of a template
3.24
sequence read
read
readout, by a specific technology more or less prone to errors, of a continuous part of a nucleic acid
molecule extracted from an organic sample
3.25
syntax field
element of data represented in the data format
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3.26
template
genomic sequence that is produced by a sequencing machine as a single unit
Note 1 to entry: A template can be made of one or more segments, being called single-end sequencing read when
it only has one segment and paired-end sequencing read when it has two segments.
3.27
transport format
set of data structures for the transport of coded information
3.28
variable
parameter either inferred from syntax fields or locally defined in a process description
4 Mathematical operators
NOTE The mathematical operators used in this document are similar to those used in the C programming
language. However, integer division with truncation and rounding are specifically defined. The bitwise operators
are defined assuming two's-complement representation of integers. Numbering and counting loops generally
begin from 0.
4.1 Arithmetic operators
+ addition
− subtraction (as a binary operator) or negation (as a unary operator)
++ increment
* multiplication
/ integer division with truncation of the result toward 0 (for example, 7/4 and −7/−4 are truncat-
ed to 1 and −7/4 and 7/−4 are truncated to −1)
4.2 Logical operators
|| logical OR
&& logical AND
! logical NOT
4.3 Relational operators
> greater than
≥ greater than or equal to
< less than
≤ less than or equal to
== equal to
!= not equal to
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4.4 Bitwise operators
& AND
| OR
>> shift right with sign extension
<< shift left with 0 fill
4.5 Assignment
= assignment operator
4.6 Unary operators
sizeof(N) size in bytes of N, where N is either a data structure or a data type
5 Structure of coded genomic data
5.1 Genomic records
The genomic record, in th
...