An ontology based query engine for querying biological sequences

91 Pages·2016·3.09 MB·English

Faculteit Bio-ingenieurswetenschappen
Academiejaar 2015-2016
An ontology based query engine for querying
biological sequences
Jim Clauwaert
Promotor: Prof. Dr. ir. Wim van Criekinge
Tutor: Martijn Devisscher
Masterproef voorgedragen tot het behalen van de graad van
Master in de bio-ingenieurswetenschappen: Cel- en genbiotechnologie

Foreword
This thesis came about during the academic year of 2015-2016, and it has been worked on as a final
project for my masters degree in bio-engineering. In many ways, this year has been very heavy. Even
though many times working on my thesis meant not working on something else I should have been
working on, I have enjoyed researching the subject and am satisfied when looking back at the work
invested. This feeling of comfort is due to many external influences that have guided and supported
me. I wish to extend my gratitude to the people that have stood by my side throughout the last
year.
First, I would like to thank Martijn Devisscher, my tutor and the spiritual father of boinq. The
rich experience obtained through my work on boinq and The Semantic Web is mainly attributed to
the positive working environment he created. I have been given both the responsibility and the trust
to handle important parts of the boinq program. This gave me not only the opportunity, but also
the ability to think for myself and introduce solutions when these presented themselves. Through
weekly appointments, I was able to follow-up and discuss work, and get directions when no path was
obvious. Through these elements I feel that I was able to contribute in the creation of boinq, and
that my input was of value. This has been both my strongest motivation and fulfilling aspect of my
thesis. I also extend my gratitude to the BioBix group. Specifically, to my promoter, Prof. Wim
Van Criekinge, for helping in making this thesis a possibility, Prof. Tim de Meyer and dr. Gerben
Menschaert, for helping me define a use case and assisting me during. I want to thank my family for
supporting me all these years. I want to thank my friends for being awesome in general. A special
thankstoMeaghanBlanchard,forbeingthefirsthelpinghandwhencorrectingandrevisingmywork,
and being there for whatever reason.
Gent, 2016
Jim Clauwaert
i

Table of Contents
Foreword i
1 Abstract 1
2 Introduction 3
3 The Semantic Web 5
3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.2 What is The Semantic Web? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3.3 RDF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
3.3.1 Structure of RDF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
3.3.2 Vocabularies of RDF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
3.4 Linked Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.4.1 Inference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.4.2 Linked databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3.5 RDF data management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.5.1 RDF formats. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.5.2 Triplestores . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
3.6 SPARQL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
3.6.1 SPARQL syntax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
4 Boinq 23
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4.2 Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
4.2.1 Data unification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
4.2.2 Data organization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
4.3 Comparison to other frameworks . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
4.3.1 Biological query building . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
4.3.2 Semantic access to sequence information. . . . . . . . . . . . . . . . . . . . 26
4.4 Material and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
5 Genomic Data Implementation 29
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
5.2 Genomic Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
5.2.1 Browser Extensible Data format . . . . . . . . . . . . . . . . . . . . . . . . 30
5.2.2 Generic Feature Format . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
5.2.3 Variant Call Format . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
5.2.4 Sequence Alignment/Map format. . . . . . . . . . . . . . . . . . . . . . . . 35
5.3 Data integration into The Semantic Web. . . . . . . . . . . . . . . . . . . . . . . . 36
5.3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
5.3.2 Basic data model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
5.3.3 Vocabularies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
5.3.4 Data models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
5.3.5 Metadata . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
5.3.6 Practical implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
5.4 Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.4.1 sparql-bed and sparql-vcf . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
5.4.2 Big data files . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
5.4.3 JBrowse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
iii
iv TABLE OF CONTENTS
6 Biological research in RDF 55
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
6.2 A biomarker for colon cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
6.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
6.2.2 Material and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
6.2.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
6.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
6.3.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
6.3.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
7 Conclusion and Future Prospects 63
A Code Examples 65
B Tables 71
C Figures 75
List of Acronyms
List of Acronyms
B
Boinq Bio ontology integrated query platform
BED Browser Extensible Data
C
CDS Coding DNA Sequence
CNV Copy Number Variations
CIMP CpG Island Methylator Phenotype
CRC Colorectal Cancer
CTD Comparative Toxicogenomics Database
D
DBMS Database Management Systems
DDBJ DNA Databank of Japan
DKO Double Knock-Out
E
EBI-EMBL The European Bioinformatics Institute
G
GDA Gene Disease Association
GFF/GFF3 General Feature Format
GFVO Genomic Feature and Variation Ontology
GMOD Generic Model Organism Database
GRC Genome Reference Consortium
GTF Genetic Transfer Object
I
v
vi TABLE OF CONTENTS
IRI International Resource Identifier
J
JSON-LD JavaScript Object Notation for Linked Data
M
MeSH Medical Subject Headings
N
NCBI National Center for Biotechnology Information
NCI National Cancer Institute
NHGRI National Human Genome Research Institute
O
OWL Web Ontology Language
R
RDF Resource Description Framework
RDFS Resource Description Framework Schema
S
SKOS Simple Knowledge Organization System
SNP Single Nucleotide Polymorphism
SO Sequence Ontology
SPARQL SPARQL Protocol and RDF Query Language
STS Spring Tool Suite
T
TCGA The Cancer Genome Atlas
U
UniProt The Universal Protein Resource
TABLE OF CONTENTS vii
URI Uniform Resource Identifier
URL Uniform Resource Locator
V
VCF Variant Call Format
W
W3C World Wide Web Consortium
WT Wild Type
WWW World Wide Web
X
XML Extensible Markup Language
XSD XML Schema Definition