Gene Disease Database

In bioinformatics, a Gene Disease Database is a systematized

collection of data, typically structured to model aspects of reality, Gene Disease Database
in a way to comprehend the underlying mechanisms of complex Classification Bioinformatics
diseases, by understanding multiple composite interactions Subclassification Databases
between phenotype-genotype relationships and gene-disease
mechanisms.[1] Gene Disease Databases integrate human gene- Type of Databases Biological
disease associations from various expert curated databases and text Subtype of Gene-
mining derived associations including Mendelian, complex and Databases Disease
environmental diseases.[2][3]

Introduction
Experts in different areas of biology and bioinformatics have been trying to comprehend the molecular
mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some illnesses, it
has become apparent that it is the right amount of animosity is made for not enough to obtain an index of
the disease-related genes but to uncover how disruptions of molecular grids in the cell give rise to disease
phenotypes.[4] Moreover, even with the unprecedented wealth of information available, obtaining such
catalogues is extremely difficult.

Genetic Broadly speaking, genetic diseases are caused by aberrations in genes or chromosomes. Many
genetic diseases are developed from before birth. Genetic disorders account for a significant number of the
health care problems in our society. Advances in the understanding of this diseases have increased both the
life span and quality of life for many of those affected by genetic disorders. Recent developments in
bioinformatics and laboratory genetics have made possible the better delineation of certain malformation
and mental retardation syndromes, so that their mode of inheritance can be understood. This information
enables the genetic counselor to predict the risk for occurrence of a large number of genetic disorders.[2]
Most genetic counseling is done, however, only after the birth of at least one affected individual has alerted
the family to their predilection for having children with a genetic disorder. The association of a single gene
to a disease is rare and a genetic disease may or may not be a transmissible disorder.[5] Some genetic
diseases are inherited from the parent's genes, but others are caused by new mutations or changes to the
DNA. In other occurrences, the same disease, for instance, some forms of carcinoma or melanoma, may
stem from an inbred condition in some people, from new changes in other people, and from non-genetic
causes in still other individuals.[6]

There are more than six thousand known single-gene disorders (monogenic), which occur in about 1 out of
every 200 births.[1] As their term suggests, these diseases are caused by a mutation in one gene. By
contrast, polygenic disorders are caused by several genes, regularly in combination with environmental
factors.[7] Examples of genetic phenotypes include Alzheimer's disease, breast cancer, leukemia, Down
syndrome, heart defects, and deafness; therefore, cataloguing to sort out all the diseases related to genes is
needed.

Challenges with creation

At different stages of
any gene disease
project, molecular
biologists need to
choose, even after
careful statistical data
analysis, which genes
or proteins to
investigate further
experimentally and
which to leave out
because of limited
resources.
Computational
methods that integrate
complex,
heterogeneous data
sets, such as
expression data,
Gene prioritization workflow of human diseases: Typical lists come from linkage
sequence information,
regions, chromosomal aberrations, association study loci, deferentially expressed
functional annotation gene lists or genes identified by sequencing variants. Alternatively, the complete
and the biomedical genome can be prioritized, but substantially more false positives would then be
literature, allow expected.
prioritizing genes for
future study in a more
informed way. Such methods can substantially increase the yield of downstream studies and are becoming
invaluable to researchers. So one of the main concerns in biological and biomedical research is to recognise
the underlying mechanisms behind this intricate genetic phenotypes. Great effort has been spent on finding
the genes related to diseases[8]

However, increasingly evidences point out that most human diseases cannot be attributed to a single gene
but arise due to complex interactions among multiple genetic variants and environmental risk factors.
Several databases have been developed storing associations between genes and diseases such as the
Comparative Toxicogenomics Database (CTD), Online Mendelian Inheritance in Man (OMIM), the
genetic Association Database (GAD) or the Disease genetic Association Database (DisGeNET). Each of
these databases focuses on different aspects of the phenotype-genotype relationship, and due to the nature
of the database curation process, they are not complete, but in a way they are fully complementary between
each other.[9]

Types of databases
Essentially, there are four types of databases: curated databases, predictive databases, literature databases
and integrative databases[1]

Curated databases

The term curated data refers to information, that may comprise the most sophisticated computational
formats for structured data, scientific updates, and curated knowledge, that has been composed and
prepared under the regulation of one or more experts considered to be qualified to engage in such an
activity[10] The implication is that the resulting database is of high quality. The contrast is with data which
may have been gathered through some automated process or using particularly low or inexpert unsupported
data quality and possibly untrustworthy.[10] Some of the most common examples include: CTD and
UNIPROT.

The Comparative Toxicogenomics Database (CTD)

The Comparative Toxicogenomics Database, helps to understand about the effects of environmental
compounds on human health by integrating data from curated scientific literature to describe biochemical
interactions with genes and proteins, and links between diseases and chemicals, and diseases and genes or
proteins.[11] CTD contains curated data defining cross-species chemical–gene/protein interactions and
chemical– and gene–disease associations to illuminate molecular mechanisms underlying variable
susceptibility and environmentally influenced diseases. These data deliver insights into complex chemical–
gene and protein interaction networks. One of the main sources in this Database is curated information from
OMIM.[11]

CTD is a unique resource where bioinformatics specialists read the scientific literature and manually curate
four types of core data:

Chemical-gene interactions
Chemical-disease associations
Gene-disease associations
Chemical-phenotype associations

The Universal Protein Resource (UNIPROT)

The Universal Protein Resource (UniProt) is an inclusive resource for protein sequence and annotation
data. It is a comprehensive, first-class and freely accessible database of protein sequence and functional
information, that has many entries being derived from genome sequencing projects. It contains a large
amount of information about the biological function of proteins derived from the study literature, which can
hint to a direct connection between gene-protein-disease.[12]

UniProt
Content
Description UniProt is the
universal protein
resource, a central
repository of
protein data
created by
combining the
Swiss-Prot,
TrEMBL and PIR-
PSD databases.
Data types Protein annotation
captured
Organisms All
Contact
Research center EMBL-EBI, UK;
SIB, Switzerland;
PIR, US.
Primary citation Ongoing and
future
developments at
the Universal
Protein
Resource[13]
Access
Data format Custom flat file,
FASTA, GFF, RDF,
XML.
Website www.uniprot.org (h
ttp://www.uniprot.o
rg)
www.uniprot.org
/news/ (http://www.
uniprot.org/news/)
Download URL www.uniprot.org
/downloads (http://
www.uniprot.org/d
ownloads) & for
downloading
complete data sets
ftp.uniprot.org (htt
p://ftp.uniprot.org)
Web service URL Yes – JAVA API
see info here (htt
p://www.ebi.ac.uk/
uniprot/remotingA
PI/) & REST see
info here (http://w
ww.uniprot.org/faq/
28)
Tools
Web Advanced search,
BLAST, ClustalO,
bulk
retrieval/download,
ID mapping
Miscellaneous
License Creative
Commons
 Attribution-
NoDerivs
Versioning Yes
Data release 4 weeks
frequency
Curation policy Yes – manual and
automatic. Rules
for automatic
annotation
generated by
database curators
and computational
algorithms.
Bookmarkable Yes – both
entities individual protein
entries and
searches

The process of database compilation and curation

The curated data may comprise a process from practical experience and literature review to web
publication of the database[14]

Predictive databases

A predictive database is one based on statistical inference. One particular approach to such inference is
known as predictive inference, but the prediction can be undertaken within any of the several approaches to
statistical inference. Indeed, one description of biostatistics is that it provides a means of transferring
knowledge about a sample of a genetic population to the whole population (genomics), and to other related
genes or genomes, which the same as prediction over time is not necessarily.[15] When information is
transferred across time, often to specific points in time, the process is known as forecasting. Three of the
main examples of databases that can be considered in this category include: The Mouse genome Database
(MGD), The Rat genome Database (RGD), OMIM and the SIFT Tool from Ensembl.[1]

The Mouse genome Database (MGD)

The Mouse genome Database (MGD) is the international community resource for integrated genetic,
genomic and biological data about the laboratory mouse. MGD provides full annotation of phenotypes and
human disease associations for mouse models (genotypes) using terms from the Mammalian Phenotype
Ontology and disease names from OMIM.[16]

The Rat Genome Database (RGD)

The Rat Genome Database (RGD) began as a collaborative effort RGD

between leading research institutions involved in rat genetic and Content
genomic research. The rat continues to be extensively used by
Description The Rat
researchers as a model organism for investigating the biology and
pathophysiology of disease. In the past several years, there has Genome
Database
been a rapid increase in rat genetic and genomic data.[17] This
explosion of information highlighted the need for a centralized Organisms Rattus
database to efficiently and effectively collect, manage, and norvegicus (rat)
distribute a rat-centric view of this data to researchers around the
Contact
world. The Rat Genome Database was created to serve as a
repository of rat genetic and genomic data, as well as mapping, Research center Medical College
strain, and physiological information. It also facilitates investigators of Wisconsin
research efforts by providing tools to search, mine, and predict this Laboratory Human
data.[17] Molecular and
Genetics Center
Data at RGD that is useful for researchers investigating disease
genes include disease annotations for rat, mouse and human genes. Authors Mary E.
Annotations are manually curated from the literature, or Shimoyama,
downloaded via automated pipelines from other disease-related PhD; Howard J.
databases. Downloaded annotations are mapped to the same Jacob, PhD
disease vocabulary used for manual annotations to provide
consistency across the dataset. RGD also maintains disease-related Primary citation PMID 25355511
quantitative phenotype data for the rat (PhenoMiner).[18] (https://pubmed.
ncbi.nlm.nih.gov/
25355511)
The Online Mendelian Inheritance in Man (OMIM)
Access
Supported by the NCBI, The Online Mendelian Inheritance in Website rgd.mcw.edu (htt
Man (OMIM) is a database that catalogues all the known diseases p://rgd.mcw.ed
with a genetic component, and predicts their relationship to u/)
relevant genes in the human genome and provides references for
Download URL RGD Data
further research and tools for genomic analysis of a catalogued
gene.[19] OMIM is a comprehensive, authoritative compendium of Release (ftp://rg
d.mcw.edu/pub/
data_release/)

The Online Mendelian

Inheritance in Man
human genes and genetic phenotypes that is freely available and Content
updated daily. The database has been used as a resource for
Description OMIM is a
predicting relevant information to inherited conditions.[19]
compendium of
human genes
Ensembl SIFT tool and genetic
phenotypes.
This one of the largest
resources available for all Organisms Human (H.
genomic and genetic Sapiens)
studies, it provides a Contact
centralized resource for
Research center NCBI
geneticists, molecular
Pathway Hogeneity vs Associated biologists and other Primary citation PMID 25398906
Genes Showing the concept that researchers studying the (https://pubmed.
diseases have large association with genomes of our own ncbi.nlm.nih.gov/
a variety of genes, a mean pathway species and other 25398906)
homogeneity values of single vertebrates and model
Access
diseases and random controls are disease organisms.
plotted for four networks binned by Ensembl is one of several Website www.ncbi.nlm
the number of associated gene well-known genome .nih.gov/omim (h
products per disease. This graph browsers for the retrieval ttps://www.ncbi.n
shows how difficult is to correlate a of genomic-disease lm.nih.gov/omi
bigger number of diseases vs information. Ensembl m)
concordance in 4 different imports
databases, hence Gene Disease variation data
Databases test these relationships The Ensembl genome database
from a variety
of different project.
sources,
Ensembl predicts the effects of variants.[21] For each
variation that is mapped to the reference genome, each
Ensembl transcript is identified that overlap the
variation. Then it uses a rule-based approach to predict
the effects that each allele of the variation may have on
the transcript. The set of consequence terms, defined by
the Sequence Ontology (SO) can be currently assigned
to each combination of an allele and a transcript. Each Content
allele of each variation may have a different effect in
different transcripts. A variety of different tools are used Description Ensembl
to predict human mutations in the Ensembl database, Contact
one of the most widely used is SIFT, that predicts
Research center Wellcome Trust Sanger
whether an amino acid substitution is likely to affect
protein function based on sequence homology and the Institute
physic-chemical similarity between the alternate amino European Bioinformatics
acids. The data provided for each amino acid Institute
substitution is a score and a qualitative prediction
Primary citation Hubbard, et al. (2002)[20]
(either 'tolerated' or 'deleterious'). The score is the
normalized probability that the amino acid change is Access
tolerated so scores near 0 are more likely to be Website www.ensembl.org (http://ww
deleterious. The qualitative prediction is derived from w.ensembl.org/)
this score such that substitutions with a score < 0.05 are
called 'deleterious' and all others are called 'tolerated'. SIFT can be applied to naturally occurring
nonsynonymous polymorphisms and laboratory-induced missense mutations, that will lead to build
relationships in phenotype characteristics, proteomics and genomics.[21]

Literature databases

This sort of databases summarize books, articles, book reviews, dissertations, and annotations about gene-
disease databases. Some of the following are examples of this type: GAD, LGHDN and BeFree Data.

Genetic Association Database (GAD)

The Genetic Association Database is an archive of human genetic association studies of complex diseases.
GAD is primarily focused on archiving information on common complex human disease rather than rare
Mendelian disorders as found in the OMIM. It includes curated summary data extracted from published
papers in peer reviewed journals on candidate gene and genome Wide Association Studies (GWAS).[22]
The GAD was frozen as of 09/01/2014 but is still available for download.[23]

Literature-derived human gene-disease network (LHGDN)

The literature-derived human gene-disease network (LHGDN) is a text mining derived database with focus
on extracting and classifying gene-disease associations with respect to several biomolecular conditions. It
uses a machine learning based algorithm to extract semantic gene-disease relations from a textual source of
interest. It is part of the Linked Life Data, of the LMU in Munchen, Germany.[1]

BeFree Data

Extracts gene-disease associations from MEDLINE abstract using the BeFree system. BeFree is composed
of a biomedical Named Entity Recognition (BioNER) module to detect diseases and genes and a relation
extraction module based on morphosyntactic information.[24]

Integrative databases

This sort of databases include Mendelian, compound and environmental diseases in an integrated gene-
disease association archive and show that the concept of modularity applies for all of them They provide a
functional analysis of diseases in case of important new biological insights, which might not be discovered
when considering each of the gene-disease associations independently. Hence, they present a suitable
framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.
The best example for this sort of database is DisGeNET.[8][25]

The Gene Disease Associations Database DisGeNET

DisGeNET is a comprehensive gene-disease association database DisGeNET

that integrates associations from several sources that covers Content
different biomedical aspects of diseases.[25] In particular, it is
Description Integrates
focused on the current knowledge of human genetic diseases
human gene-
including Mendelian, complex and environmental diseases. To
assess the concept of modularity of human diseases, this database disease
performs a systematic study of the emergent properties of human associations
gene-disease networks by means of network topology and Data types Associations
functional annotation analysis.[1] The results indicate a highly captured Database
shared genetic origin of human diseases and show that for most
Organisms Human (H.
diseases, including Mendelian, complex and environmental
diseases, functional modules exist. Moreover, a core set of Sapiens)
biological pathways is found to be associated with most human Contact
diseases. Obtaining similar results when studying clusters of Research center Research
diseases, the findings in this database suggest that related diseases
Programme on
might arise due to dysfunction of common biological processes in
Biomedical
the cell. The network analysis of this integrated database points out
that data integration is needed to obtain a comprehensive view of Informatics
the genetic landscape of human diseases and that the genetic origin (GRIB) IMIM-
of complex diseases is much more common than expected.[1] UPF
Laboratory Integrative
Biomedical
Informatics
Group
Authors Ferran Sanz and
Laura I. Furlong
(Pinero et al,
2015)
Primary citation PMID 25877637
(https://pubmed.
ncbi.nlm.nih.gov/
25877637)
Access
Website www.disgenet
.org (http://www.
disgenet.org/)
Miscellaneous
Data release annual
frequency
Version 3
DisGeNET gene-disease association ontology
The description of each association type in this ontology is: #Therapeutic
Association: The gene/protein has a therapeutic role in the amelioration of the
disease. #Biomarker Association: The gene/protein either plays a role in the etiology
of the disease (e.g. participates in the molecular mechanism that leads to disease) or
is a biomarker for a disease. #Genetic Variation Association: Used when a sequence
variation (a mutation, a SNP) is associated to the disease phenotype, but there is still
no evidence to say that the variation causes the disease. In some cases the
presence of the variants increase the susceptibility to the disease. In general, the
NCBI SNP identifiers are provided. #Altered Expression Association: Alterations in
the function of the protein by means of altered expression of the gene are associated
with the disease phenotype. #Post-translational Modification Association: Alterations
in the function of the protein by means of post-translational modifications
(methylation or phosphorylation of the protein) are associated with the disease
phenotype. [1]

Some use cases

Some of the most interesting cases using Gene-Disease Databases can be found in the following
papers:[1][8]

Santiago, Jose A.; Potashkin, Judith A. (2014). "A network approach to clinical intervention
in neurodegenerative diseases". Trends in Molecular Medicine. 20 (12): 694–703.
doi:10.1016/j.molmed.2014.10.002 (https://doi.org/10.1016%2Fj.molmed.2014.10.002).
PMID 25455073 (https://pubmed.ncbi.nlm.nih.gov/25455073).
Kaikkonen, Minna U.; Niskanen, Henri; Romanoski, Casey E.; Kansanen, Emilia; Kivelä,
Annukka M.; Laitalainen, Jarkko; Heinz, Sven; Benner, Christopher; Glass, Christopher K.;
Ylä-Herttuala, Seppo (2014). "Control of VEGF-A transcriptional programs by pausing and
genomic compartmentalization" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227755).
Nucleic Acids Research. 42 (20): 12570–12584. doi:10.1093/nar/gku1036 (https://doi.org/10.
1093%2Fnar%2Fgku1036). PMC 4227755 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4
227755). PMID 25352550 (https://pubmed.ncbi.nlm.nih.gov/25352550).
Grosdidier, Solène; Ferrer, Antoni; Faner, Rosa; Piñero, Janet; Roca, Josep; Cosío, Borja;
Agustí, Alvar; Gea, Joaquim; Sanz, Ferran; Furlong, Laura I. (2014). "Network medicine
analysis of COPD multimorbidities" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC417742
1). Respiratory Research. 15 (1): 111. doi:10.1186/s12931-014-0111-4 (https://doi.org/10.11
86%2Fs12931-014-0111-4). PMC 4177421 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC
4177421). PMID 25248857 (https://pubmed.ncbi.nlm.nih.gov/25248857).
Cristiano, Francesca; Veltri, Pierangelo (2014). "An R-based tool for miRNA data analysis
and correlation with clinical ontologies". Proceedings of the 5th ACM Conference on
Bioinformatics, Computational Biology, and Health Informatics - BCB '14. pp. 768–773.
doi:10.1145/2649387.2660847 (https://doi.org/10.1145%2F2649387.2660847).
ISBN 9781450328944. S2CID 17123912 (https://api.semanticscholar.org/CorpusID:171239
12).
Gallagher, Suzanne Renick; Dombrower, Micah; Goldberg, Debra S. (2014). "Using 2-node
hypergraph clustering coefficients to analyze disease-gene networks". Proceedings of the
5th ACM Conference on Bioinformatics, Computational Biology, and Health Informatics -
BCB '14. pp. 647–648. doi:10.1145/2649387.2660817 (https://doi.org/10.1145%2F2649387.
2660817). ISBN 9781450328944. S2CID 30593231 (https://api.semanticscholar.org/CorpusI
D:30593231).
Mannil, Deepthi; Vogt, Ingo; Prinz, Jeanette; Campillos, Monica (2015). "Organ system
heterogeneity DB: A database for the visualization of phenotypes at the organ system level"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384019). Nucleic Acids Research. 43
(Database issue): D900–D906. doi:10.1093/nar/gku948 (https://doi.org/10.1093%2Fnar%2F
gku948). PMC 4384019 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384019).
PMID 25313158 (https://pubmed.ncbi.nlm.nih.gov/25313158).
Vogt, Ingo; Prinz, Jeanette; Campillos, Mónica (2014). "Molecularly and clinically related
drugs and diseases are enriched in phenotypically similar drug-disease pairs" (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC4165361). Genome Medicine. 6 (7): 52.
doi:10.1186/s13073-014-0052-z (https://doi.org/10.1186%2Fs13073-014-0052-z).
PMC 4165361 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165361). PMID 25276232
(https://pubmed.ncbi.nlm.nih.gov/25276232).
Santiago, Jose A.; Potashkin, Judith A. (2014). "System-based approaches to decode the
molecular links in Parkinson's disease and diabetes". Neurobiology of Disease. 72: 84–91.
doi:10.1016/j.nbd.2014.03.019 (https://doi.org/10.1016%2Fj.nbd.2014.03.019).
PMID 24718034 (https://pubmed.ncbi.nlm.nih.gov/24718034). S2CID 41944859 (https://api.s
emanticscholar.org/CorpusID:41944859).
Lee, In-Hee; Lee, Kyungjoon; Hsing, Michael; Choe, Yongjoon; Park, Jin-Ho; Kim, Shu Hee;
Bohn, Justin M.; Neu, Matthew B.; Hwang, Kyu-Baek; Green, Robert C.; Kohane, Isaac S.;
Kong, Sek Won (2014). "Prioritizing Disease-Linked Variants, Genes, and Pathways with an
Interactive Whole-Genome Analysis Pipeline" (https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C4130156). Human Mutation. 35 (5): 537–547. doi:10.1002/humu.22520 (https://doi.org/10.1
002%2Fhumu.22520). PMC 4130156 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41301
56). PMID 24478219 (https://pubmed.ncbi.nlm.nih.gov/24478219).
Liu, Ming-Xi; Chen, Xing; Chen, Geng; Cui, Qing-Hua; Yan, Gui-Ying (2014). "A
Computational Framework to Infer Human Disease-Associated Long Noncoding RNAs" (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879311). PLOS ONE. 9 (1): e84408.
Bibcode:2014PLoSO...984408L (https://ui.adsabs.harvard.edu/abs/2014PLoSO...984408L).
doi:10.1371/journal.pone.0084408 (https://doi.org/10.1371%2Fjournal.pone.0084408).
PMC 3879311 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879311). PMID 24392133
(https://pubmed.ncbi.nlm.nih.gov/24392133).
Zhao, Yilei; Wang, Chen; Wu, Jianwei; Wang, Yan; Zhu, Wenliang; Zhang, Yong; Du, Zhimin
(2013). "Choline Protects Against Cardiac Hypertrophy Induced by Increased After-load" (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596715). International Journal of Biological
Sciences. 9 (3): 295–302. doi:10.7150/ijbs.5976 (https://doi.org/10.7150%2Fijbs.5976).
PMC 3596715 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596715). PMID 23493786
(https://pubmed.ncbi.nlm.nih.gov/23493786).
 Koczor, Christopher A.; Lee, Eva K.; Torres, Rebecca A.; Boyd, Amy; Vega, J. David; Uppal,
Karan; Yuan, Fan; Fields, Earl J.; Samarel, Allen M.; Lewis, William (2013). "Detection of
differentially methylated gene promoters in failing and nonfailing human left ventricle
myocardium using computation analysis" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC37
27018). Physiological Genomics. 45 (14): 597–605.
doi:10.1152/physiolgenomics.00013.2013 (https://doi.org/10.1152%2Fphysiolgenomics.000
13.2013). PMC 3727018 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3727018).
PMID 23695888 (https://pubmed.ncbi.nlm.nih.gov/23695888).
Gu, Ying; Liu, Guang-Hui; Plongthongkum, Nongluk; Benner, Christopher; Yi, Fei; Qu, Jing;
Suzuki, Keiichiro; Yang, Jiping; Zhang, Weiqi; Li, Mo; Montserrat, Nuria; Crespo, Isaac; Del
Sol, Antonio; Esteban, Concepcion Rodriguez; Zhang, Kun; Izpisua Belmonte, Juan Carlos
(2014). "Global DNA methylation and transcriptional analyses of human ESC-derived
cardiomyocytes" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938846). Protein & Cell. 5
(1): 59–68. doi:10.1007/s13238-013-0016-x (https://doi.org/10.1007%2Fs13238-013-0016-
x). PMC 3938846 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938846).
PMID 24474197 (https://pubmed.ncbi.nlm.nih.gov/24474197).
Galhardo, Mafalda; Sinkkonen, Lasse; Berninger, Philipp; Lin, Jake; Sauter, Thomas;
Heinäniemi, Merja (2014). "Integrated analysis of transcript-level regulation of metabolism
reveals disease-relevant nodes of the human metabolic network" (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC3919568). Nucleic Acids Research. 42 (3): 1474–1496.
doi:10.1093/nar/gkt989 (https://doi.org/10.1093%2Fnar%2Fgkt989). PMC 3919568 (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC3919568). PMID 24198249 (https://pubmed.ncbi.nlm.
nih.gov/24198249).
Tieri, Paolo; Termanini, Alberto; Bellavista, Elena; Salvioli, Stefano; Capri, Miriam;
Franceschi, Claudio (2012). "Charting the NF-κB Pathway Interactome Map" (https://www.nc
bi.nlm.nih.gov/pmc/articles/PMC3293857). PLOS ONE. 7 (3): e32678.
Bibcode:2012PLoSO...732678T (https://ui.adsabs.harvard.edu/abs/2012PLoSO...732678T).
doi:10.1371/journal.pone.0032678 (https://doi.org/10.1371%2Fjournal.pone.0032678).
PMC 3293857 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3293857). PMID 22403694
(https://pubmed.ncbi.nlm.nih.gov/22403694).

Remarks about the future in Gene Disease Databases

The completion of the human genome has changed the way the
search for disease genes is performed. In the past, the approach was
to focus on one or a few genes at a time. Now, projects like the
DisGeNET exemplify the efforts to systematically analyze all the
gene alterations involved in a single or multiple diseases.[26] The
next step is to produce a complete picture of the mechanistic
aspects of the diseases and the design of drugs against them. For
that, a combination of two approaches will be needed: a systematic
search and in-depth study of each gene. The future of the field will
be defined by new techniques to integrate large bodies of data from
different sources and to incorporate functional information into the
analysis of large-scale data generated by bioinformatics studies.[1] Relationships in Gene Diseases

Bioinformatics is both a term for the body of biological gene

disease studies that use computer programming as part of their methodology, as well as a reference to
specific analysis pipelines that are repeatedly used, particularly in the fields of genetics and genomics.[1]
Common uses of bioinformatics include the identification of candidate genes and nucleotides, SNPs. Often,
such identification is made with the aim of better understanding the genetic basis of disease, unique
adaptations, desirable properties, or differences between populations. In a less formal way, bioinformatics
also tries to understand the organisational principles within nucleic acid and protein sequences.[1]

The response of bioinformatics to new experimental techniques brings a new perspective into the analysis
of the experimental data, as demonstrated by the advances in the analysis of information from gene disease
databases and other technologies. It is expected that this trend will continue with novel approaches to
respond to new techniques, such as next-generation sequencing technologies. For instance, the availability
of large numbers of individual human genomes will promote the development of computational analyses of
rare variants, including the statistical mining of their relations to lifestyles, drug interactions and other
factors.[1] Biomedical research will also be driven by our ability to efficiently mine the large body of
existing and continuously generated biomedical data. Text-mining techniques, in particular, when combined
with other molecular data, can provide information about gene mutations and interactions and will become
crucial to stay ahead of the exponential growth of data generated in biomedical research. Another field that
is benefiting from the advances in mining and integration of molecular, clinical and drug analysis is
pharmacogenomics. In silico studies of the relationships between human variations and their effect on
diseases will be key to the development of personalized medicine.[8] In summary, Gene Disease Databases
have already transformed the search for disease genes and has the potential to become a crucial component
of other areas of medical research.[1]

See also
Biology portal

Biodiversity informatics
Bioinformatics companies
Biomedicine
Computational biology
Computational biomodeling
Computational genomics
Disease gene identification
European Bioinformatics Institute
Functional genomics
Health informatics
Human Genome Project
Integrative bioinformatics
International Society for Computational Biology
Jumping library
List of bioinformatics journals
List of biological databases
List of open-source bioinformatics software
Pathology
Phylogenetics
Structural bioinformatics

References
1. A. Bauer-Mehren, "Gene-Disease network Analysis Reveals Functional Modules in
 Mendelian, Complex and Environmental diseases," PLOS One, pp. 1-3, 2011.
2. Botstein, D (2003). "Discovering genotypes underlying human phenotypes: past successes
for Mendelian disease, future approaches for complex disease". Nature Genetics. 33 (1):
228–237. doi:10.1038/ng1090 (https://doi.org/10.1038%2Fng1090). PMID 12610532 (https://
pubmed.ncbi.nlm.nih.gov/12610532). S2CID 10599219 (https://api.semanticscholar.org/Cor
pusID:10599219).
3. Wren JD, Bateman A (2008). "Databases, data tombs and dust in the wind" (https://doi.org/1
0.1093%2Fbioinformatics%2Fbtn464). Bioinformatics. 24 (19): 2127–8.
doi:10.1093/bioinformatics/btn464 (https://doi.org/10.1093%2Fbioinformatics%2Fbtn464).
PMID 18819940 (https://pubmed.ncbi.nlm.nih.gov/18819940).
4. American Medical Informatics Association, "American Medical Informatics Association
Strategic Plan," August 2011. [Online]. Available: http://www.amia.org/inside/stratplan/.
[Accessed 15 October 2014].
5. Oti, M (2007). "The modular nature of genetic diseases". Clinical Genetics. 71 (1): 1–11.
doi:10.1111/j.1399-0004.2006.00708.x (https://doi.org/10.1111%2Fj.1399-0004.2006.00708.
x). PMID 17204041 (https://pubmed.ncbi.nlm.nih.gov/17204041). S2CID 24615025 (https://a
pi.semanticscholar.org/CorpusID:24615025).
6. Davis, A.; King, B. (2011). "The Comparative Toxicogenomics Database: update 2011" (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013756). Nucleic Acids Res. 39 (1): 1067–
1072. doi:10.1093/nar/gkq813 (https://doi.org/10.1093%2Fnar%2Fgkq813). PMC 3013756
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013756). PMID 20864448 (https://pubmed.
ncbi.nlm.nih.gov/20864448).
7. Davis, A.; Wiegers, T. (2013). "Text Mining Effectively Scores and Ranks the Literature for
Improving Chemical-Gene-Disease Curation at the Comparative Toxicogenomics Database"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629079). PLOS ONE. 8 (4): 1–29.
Bibcode:2013PLoSO...858201D (https://ui.adsabs.harvard.edu/abs/2013PLoSO...858201D).
doi:10.1371/journal.pone.0058201 (https://doi.org/10.1371%2Fjournal.pone.0058201).
PMC 3629079 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3629079). PMID 23613709
(https://pubmed.ncbi.nlm.nih.gov/23613709).
8. Bauer-Mehren, A.; Rautscha, M. (2010). "DisGeNET: a Cytoscape plugin to visualize,
integrate, search and analyze gene–disease networks" (https://doi.org/10.1093%2Fbioinfor
matics%2Fbtq538). Bioinformatics. 26 (22): 2924–2926. doi:10.1093/bioinformatics/btq538
(https://doi.org/10.1093%2Fbioinformatics%2Fbtq538). PMID 20861032 (https://pubmed.ncb
i.nlm.nih.gov/20861032).
9. Vogt, I. (2014). "Systematic analysis of gene properties influencing organ system
phenotypes in mammalian perturbations" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46
09011). Bioinformatics. 30 (21): 3093–3100. doi:10.1093/bioinformatics/btu487 (https://doi.or
g/10.1093%2Fbioinformatics%2Fbtu487). PMC 4609011 (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC4609011). PMID 25061072 (https://pubmed.ncbi.nlm.nih.gov/25061072).
10. Buneman, P. (2008). "Curated Databases". Bibliometrics. 978 (1): 152–162.
11. Murphy, C.; Davis, A. (2009). "Comparative Toxicogenomics Database: a knowledgebase
and discovery tool for chemical–gene–disease networks" (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC2686584). Bioinformatics. 37 (1): 786–792. doi:10.1093/nar/gkn580 (https://doi.
org/10.1093%2Fnar%2Fgkn580). PMC 2686584 (https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC2686584). PMID 18782832 (https://pubmed.ncbi.nlm.nih.gov/18782832).
12. Uniprot, Consortium (2008). "The Universal Protein Resource (UniProt)" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC1669721). Nucleic Acids Research. 36 (1): 190–195.
doi:10.1093/nar/gkm895 (https://doi.org/10.1093%2Fnar%2Fgkm895). PMC 1669721 (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC1669721). PMID 18045787 (https://pubmed.ncbi.
nlm.nih.gov/18045787).
13. Uniprot, C. (2010). "Ongoing and future developments at the Universal Protein Resource" (ht
tps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013648). Nucleic Acids Research. 39
(Database issue): D214–D219. doi:10.1093/nar/gkq1020 (https://doi.org/10.1093%2Fnar%2
Fgkq1020). PMC 3013648 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3013648).
PMID 21051339 (https://pubmed.ncbi.nlm.nih.gov/21051339).
14. K. Brown, "Online Predicted human Interaction Database," Bioinformatics, vol. 21, no. 9, pp.
2076-2082, 2005.
15. S. Hunter and P. Jones, "InterPro in 2011: new developments in the family and domain
prediction database," Nucleic Acids Research, vol. 10, no. 1, pp. 12-22, 2011
16. C. Bult and J. Eppig, "The Mouse genome Database (MGD): mouse biology and model
systems," Nucleic Acids Research, vol. 36, no. 1, pp. 724-728, 2007
17. M. Dwinell, E. Worthey and S. M, "The Rat genome Database 2009: variation, ontologies
and pathways," Nucleic Acids Research, vol. 37, no. 1, pp. 744-749, 2009
18. Shimoyama M, De Pons J, Hayman GT, et al. (2015). "The Rat Genome Database 2015:
genomic, phenotypic and environmental variations and disease" (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC4383884). Nucleic Acids Research. 43 (Database issue): D743–50.
doi:10.1093/nar/gku1026 (https://doi.org/10.1093%2Fnar%2Fgku1026). PMC 4383884 (http
s://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383884). PMID 25355511 (https://pubmed.ncbi.
nlm.nih.gov/25355511).
19. A. Homosh, "Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human
genes and genetic disorders," Nucleic Acids Research, vol. 33, no. 1, pp. 514-517, 2005
20. Hubbard T, et al. (January 2002). "The Ensembl genome database project" (https://www.ncb
i.nlm.nih.gov/pmc/articles/PMC99161). Nucleic Acids Research. 30 (1): 38–41.
doi:10.1093/nar/30.1.38 (https://doi.org/10.1093%2Fnar%2F30.1.38). PMC 99161 (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC99161). PMID 11752248 (https://pubmed.ncbi.nlm.ni
h.gov/11752248).
21. P. Flicek and M. Ridwan, "Ensembl 2012," Nucleic Acids Research, vol. 40, no. 1, pp. 84-90,
2012
22. Becker, K.; Barnes, K. (2004). "The genetic Association Database" (https://doi.org/10.1038%
2Fng0504-431). Nature Genetics. 36 (5): 431–432. doi:10.1038/ng0504-431 (https://doi.org/
10.1038%2Fng0504-431). PMID 15118671 (https://pubmed.ncbi.nlm.nih.gov/15118671).
23. https://geneticassociationdb.nih.gov/
24. Bravo, A; et al. (2014). "Extraction of relations between genes and diseases from text and
large-scale data analysis: implications for translational research" (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC4466840). BMC Bioinformatics. 16 (1): 55. doi:10.1186/s12859-015-
0472-9 (https://doi.org/10.1186%2Fs12859-015-0472-9). PMC 4466840 (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC4466840). PMID 25886734 (https://pubmed.ncbi.nlm.nih.gov/25
886734).
25. Piñero; et al. (2015). "DisGeNET: a discovery platform for the dynamical exploration of
human diseases and their genes" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397996).
Database. 2015: bav028. doi:10.1093/database/bav028 (https://doi.org/10.1093%2Fdatabas
e%2Fbav028). PMC 4397996 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397996).
PMID 25877637 (https://pubmed.ncbi.nlm.nih.gov/25877637).
26. Oti, M (2006). "Predicting disease genes using protein-protein interactions" (https://www.ncb
i.nlm.nih.gov/pmc/articles/PMC2564594). J. Med. Genet. 43 (8): 691–698.
doi:10.1136/jmg.2006.041376 (https://doi.org/10.1136%2Fjmg.2006.041376). PMC 2564594
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564594). PMID 16611749 (https://pubmed.
ncbi.nlm.nih.gov/16611749).
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