Professional Documents
Culture Documents
Contents
Introduction
History
Sequences
Goals
Relation to other fields
Sequence analysis
DNA sequencing
Sequence assembly
Genome annotation
Computational evolutionary biology
Comparative genomics
Pan genomics
Genetics of disease
Analysis of mutations in cancer
Gene and protein expression
Analysis of gene expression
Analysis of protein expression
Analysis of regulation
Analysis of cellular organization
Microscopy and image analysis
Protein localization
Nuclear organization of chromatin
Structural bioinformatics
Network and systems biology
Molecular interaction networks
Others
Literature analysis
High-throughput image analysis
High-throughput single cell data analysis
Biodiversity informatics
Ontologies and data integration
Databases
Software and tools
Open-source bioinformatics software
Web services in bioinformatics
Bioinformatics workflow management systems
BioCompute and BioCompute Objects
Education platforms
Conferences
See also
References
Further reading
External links
Introduction
Bioinformatics has become an important part of many areas of biology. In experimental molecular biology, bioinformatics
techniques such as image and signal processing allow extraction of useful results from large amounts of raw data. In the field of
genetics, it aids in sequencing and annotating genomes and their observed mutations. It plays a role in the text mining of
biological literature and the development of biological and gene ontologies to organize and query biological data. It also plays a
role in the analysis of gene and protein expression and regulation. Bioinformatics tools aid in the comparison of genetic and
genomic data and more generally in the understanding of evolutionary aspects of molecular biology. At a more integrative level,
it helps analyze and catalogue the biological pathways and networks that are an important part of systems biology. In structural
biology, it aids in the simulation and modeling of DNA,[2] RNA,[2][3] proteins[4] as well as biomolecular interactions.[5][6][7][8]
History
Historically, the term bioinformatics did not mean what it means today. Paulien Hogeweg and Ben Hesper coined it in 1970 to
refer to the study of information processes in biotic systems.[9][10][11] This definition placed bioinformatics as a field parallel to
biochemistry (the study of chemical processes in biological systems).[9]
Sequences
Computers became essential in molecular biology when protein sequences became available after Frederick Sanger determined
the sequence of insulin in the early 1950s. Comparing multiple sequences manually turned out to be impractical. A pioneer in the
field was Margaret Oakley Dayhoff.[12] She compiled one of the first protein sequence databases, initially published as books[13]
and pioneered methods of sequence alignment and molecular evolution.[14] Another early contributor to bioinformatics was Elvin
A. Kabat, who pioneered biological sequence analysis in 1970 with his comprehensive volumes of antibody sequences released
with Tai Te Wu between 1980 and 1991.[15]
Goals
To study how normal cellular activities are altered in different disease states, the
biological data must be combined to form a comprehensive picture of these
activities. Therefore, the field of bioinformatics has evolved such that the most Sequences of genetic material are
pressing task now involves the analysis and interpretation of various types of frequently used in bioinformatics and
data. This includes nucleotide and amino acid sequences, protein domains, and are easier to manage using
protein structures.[16] The actual process of analyzing and interpreting data is computers than manually.
referred to as computational biology. Important sub-disciplines within
bioinformatics and computational biology include:
Development and implementation of computer programs that enable efficient access to, use and management of,
various types of information
Development of new algorithms (mathematical formulas) and statistical measures that assess relationships
among members of large data sets. For example, there are methods to locate a gene within a sequence, to
predict protein structure and/or function, and to cluster protein sequences into families of related sequences.
The primary goal of bioinformatics is to increase the understanding of biological processes. What sets it apart from other
approaches, however, is its focus on developing and applying computationally intensive techniques to achieve this goal.
Examples include: pattern recognition, data mining, machine learning algorithms, and visualization. Major research efforts in the
field include sequence alignment, gene finding, genome assembly, drug design, drug discovery, protein structure alignment,
protein structure prediction, prediction of gene expression and protein–protein interactions, genome-wide association studies, the
modeling of evolution and cell division/mitosis.
Bioinformatics now entails the creation and advancement of databases, algorithms, computational and statistical techniques, and
theory to solve formal and practical problems arising from the management and analysis of biological data.
Over the past few decades, rapid developments in genomic and other molecular research technologies and developments in
information technologies have combined to produce a tremendous amount of information related to molecular biology.
Bioinformatics is the name given to these mathematical and computing approaches used to glean understanding of biological
processes.
Common activities in bioinformatics include mapping and analyzing DNA and protein sequences, aligning DNA and protein
sequences to compare them, and creating and viewing 3-D models of protein structures.
Analyzing biological data to produce meaningful information involves writing and running software programs that use algorithms
from graph theory, artificial intelligence, soft computing, data mining, image processing, and computer simulation. The
algorithms in turn depend on theoretical foundations such as discrete mathematics, control theory, system theory, information
theory, and statistics.
Sequence analysis
Since the Phage Φ-X174
was sequenced in 1977,[17]
the DNA sequences of
thousands of organisms
have been decoded and
stored in databases. This
The sequences of different genes or proteins may be aligned side-by-side to measure sequence information is
their similarity. This alignment compares protein sequences and genomic sequences analyzed to determine
containing WPP domains. genes that encode proteins,
RNA genes, regulatory
sequences, structural
motifs, and repetitive sequences. A comparison of genes within a species or between different species can show similarities
between protein functions, or relations between species (the use of molecular systematics to construct phylogenetic trees). With
the growing amount of data, it long ago became impractical to analyze DNA sequences manually. Today, computer programs
such as BLAST are used daily to search sequences from more than 260 000 organisms, containing over 190 billion
nucleotides.[18] These programs can compensate for mutations (exchanged, deleted or inserted bases) in the DNA sequence, to
identify sequences that are related, but not identical. A variant of this sequence alignment is used in the sequencing process itself.
For the special task of taxonomic classification of sequence snippets, modern k-mer based software like Kraken achieves
throughput unreachable by alignment methods.
DNA sequencing
Before sequences can be analyzed they have to be obtained. DNA sequencing is still a non-trivial problem as the raw data may be
noisy or afflicted by weak signals. Algorithms have been developed for base calling for the various experimental approaches to
DNA sequencing.
Sequence assembly
Most DNA sequencing techniques produce short fragments of sequence that need to be assembled to obtain complete gene or
genome sequences. The so-called shotgun sequencing technique (which was used, for example, by The Institute for Genomic
Research (TIGR) to sequence the first bacterial genome, Haemophilus influenzae)[19] generates the sequences of many thousands
of small DNA fragments (ranging from 35 to 900 nucleotides long, depending on the sequencing technology). The ends of these
fragments overlap and, when aligned properly by a genome assembly program, can be used to reconstruct the complete genome.
Shotgun sequencing yields sequence data quickly, but the task of assembling the fragments can be quite complicated for larger
genomes. For a genome as large as the human genome, it may take many days of CPU time on large-memory, multiprocessor
computers to assemble the fragments, and the resulting assembly usually contains numerous gaps that must be filled in later.
Shotgun sequencing is the method of choice for virtually all genomes sequenced today, and genome assembly algorithms are a
critical area of bioinformatics research.
Genome annotation
In the context of genomics, annotation is the process of marking the genes and other biological features in a DNA sequence. This
process needs to be automated because most genomes are too large to annotate by hand, not to mention the desire to annotate as
many genomes as possible, as the rate of sequencing has ceased to pose a bottleneck. Annotation is made possible by the fact that
genes have recognisable start and stop regions, although the exact sequence found in these regions can vary between genes.
The first description of a comprehensive genome annotation system was published in 1995 [19] by the team at The Institute for
Genomic Research that performed the first complete sequencing and analysis of the genome of a free-living organism, the
bacterium Haemophilus influenzae.[19] Owen White designed and built a software system to identify the genes encoding all
proteins, transfer RNAs, ribosomal RNAs (and other sites) and to make initial functional assignments. Most current genome
annotation systems work similarly, but the programs available for analysis of genomic DNA, such as the GeneMark program
trained and used to find protein-coding genes in Haemophilus influenzae, are constantly changing and improving.
Following the goals that the Human Genome Project left to achieve after its closure in 2003, a new project developed by the
National Human Genome Research Institute in the U.S appeared. The so-called ENCODE project is a collaborative data
collection of the functional elements of the human genome that uses next-generation DNA-sequencing technologies and genomic
tiling arrays, technologies able to automatically generate large amounts of data at a dramatically reduced per-base cost but with
the same accuracy (base call error) and fidelity (assembly error).
trace the evolution of a large number of organisms by measuring changes in their DNA, rather than through
physical taxonomy or physiological observations alone,
compare entire genomes, which permits the study of more complex evolutionary events, such as gene
duplication, horizontal gene transfer, and the prediction of factors important in bacterial speciation,
build complex computational population genetics models to predict the outcome of the system over time[20]
track and share information on an increasingly large number of species and organisms
Future work endeavours to reconstruct the now more complex tree of life.
The area of research within computer science that uses genetic algorithms is sometimes confused with computational
evolutionary biology, but the two areas are not necessarily related.
Comparative genomics
The core of comparative genome analysis is the establishment of the correspondence between genes (orthology analysis) or other
genomic features in different organisms. It is these intergenomic maps that make it possible to trace the evolutionary processes
responsible for the divergence of two genomes. A multitude of evolutionary events acting at various organizational levels shape
genome evolution. At the lowest level, point mutations affect individual nucleotides. At a higher level, large chromosomal
segments undergo duplication, lateral transfer, inversion, transposition, deletion and insertion.[21] Ultimately, whole genomes are
involved in processes of hybridization, polyploidization and endosymbiosis, often leading to rapid speciation. The complexity of
genome evolution poses many exciting challenges to developers of mathematical models and algorithms, who have recourse to a
spectrum of algorithmic, statistical and mathematical techniques, ranging from exact, heuristics, fixed parameter and
approximation algorithms for problems based on parsimony models to Markov chain Monte Carlo algorithms for Bayesian
analysis of problems based on probabilistic models.
Many of these studies are based on the detection of sequence homology to assign sequences to protein families.[22]
Pan genomics
Pan genomics is a concept introduced in 2005 by Tettelin and Medini which eventually took root in bioinformatics. Pan genome
is the complete gene repertoire of a particular taxonomic group: although initially applied to closely related strains of a species, it
can be applied to a larger context like genus, phylum etc. It is divided in two parts- The Core genome: Set of genes common to all
the genomes under study (These are often housekeeping genes vital for survival) and The Dispensable/Flexible Genome: Set of
genes not present in all but one or some genomes under study. A bioinformatics tool BPGA can be used to characterize the Pan
Genome of bacterial species.[23]
Genetics of disease
With the advent of next-generation sequencing we are obtaining enough sequence data to map the genes of complex diseases
infertility,[24] breast cancer[25] or Alzheimer's disease.[26] Genome-wide association studies are a useful approach to pinpoint the
mutations responsible for such complex diseases.[27] Through these studies, thousands of DNA variants have been identified that
are associated with similar diseases and traits.[28] Furthermore, the possibility for genes to be used at prognosis, diagnosis or
treatment is one of the most essential applications. Many studies are discussing both the promising ways to choose the genes to be
used and the problems and pitfalls of using genes to predict disease presence or prognosis.[29]
Two important principles can be used in the analysis of cancer genomes bioinformatically pertaining to the identification of
mutations in the exome. First, cancer is a disease of accumulated somatic mutations in genes. Second cancer contains driver
mutations which need to be distinguished from passengers.[30]
With the breakthroughs that this next-generation sequencing technology is providing to the field of Bioinformatics, cancer
genomics could drastically change. These new methods and software allow bioinformaticians to sequence many cancer genomes
quickly and affordably. This could create a more flexible process for classifying types of cancer by analysis of cancer driven
mutations in the genome. Furthermore, tracking of patients while the disease progresses may be possible in the future with the
sequence of cancer samples.[31]
Another type of data that requires novel informatics development is the analysis of lesions found to be recurrent among many
tumors.
Analysis of regulation
Gene regulation is the complex orchestration of events by which a signal, potentially an extracellular signal such as a hormone,
eventually leads to an increase or decrease in the activity of one or more proteins. Bioinformatics techniques have been applied to
explore various steps in this process.
For example, gene expression can be regulated by nearby elements in the genome. Promoter analysis involves the identification
and study of sequence motifs in the DNA surrounding the coding region of a gene. These motifs influence the extent to which
that region is transcribed into mRNA. Enhancer elements far away from the promoter can also regulate gene expression, through
three-dimensional looping interactions. These interactions can be determined by bioinformatic analysis of chromosome
conformation capture experiments.
Expression data can be used to infer gene regulation: one might compare microarray data from a wide variety of states of an
organism to form hypotheses about the genes involved in each state. In a single-cell organism, one might compare stages of the
cell cycle, along with various stress conditions (heat shock, starvation, etc.). One can then apply clustering algorithms to that
expression data to determine which genes are co-expressed. For example, the upstream regions (promoters) of co-expressed genes
can be searched for over-represented regulatory elements. Examples of clustering algorithms applied in gene clustering are k-
means clustering, self-organizing maps (SOMs), hierarchical clustering, and consensus clustering methods.
Protein localization
The localization of proteins helps us to evaluate the role of a protein. For instance, if a protein is found in the nucleus it may be
involved in gene regulation or splicing. By contrast, if a protein is found in mitochondria, it may be involved in respiration or
other metabolic processes. Protein localization is thus an important component of protein function prediction. There are well
developed protein subcellular localization prediction resources available, including protein subcellular location databases, and
prediction tools.[34][35]
Structural bioinformatics
Protein structure prediction is another important application of bioinformatics.
The amino acid sequence of a protein, the so-called primary structure, can be
easily determined from the sequence on the gene that codes for it. In the vast
majority of cases, this primary structure uniquely determines a structure in its
native environment. (Of course, there are exceptions, such as the bovine
spongiform encephalopathy (mad cow disease) prion.) Knowledge of this
structure is vital in understanding the function of the protein. Structural
information is usually classified as one of secondary, tertiary and quaternary
structure. A viable general solution to such predictions remains an open
problem. Most efforts have so far been directed towards heuristics that work
most of the time.
One of the key ideas in bioinformatics is the notion of homology. In the genomic
branch of bioinformatics, homology is used to predict the function of a gene: if
3-dimensional protein structures
the sequence of gene A, whose function is known, is homologous to the
such as this one are common
subjects in bioinformatic analyses. sequence of gene B, whose function is unknown, one could infer that B may
share A's function. In the structural branch of bioinformatics, homology is used
to determine which parts of a protein are important in structure formation and
interaction with other proteins. In a technique called homology modeling, this information is used to predict the structure of a
protein once the structure of a homologous protein is known. This currently remains the only way to predict protein structures
reliably.
One example of this is hemoglobin in humans and the hemoglobin in legumes (leghemoglobin), which are distant relatives from
the same protein superfamily. Both serve the same purpose of transporting oxygen in the organism. Although both of these
proteins have completely different amino acid sequences, their protein structures are virtually identical, which reflects their near
identical purposes and shared ancestor.[37]
Other techniques for predicting protein structure include protein threading and de novo (from scratch) physics-based modeling.
Another aspect of structural bioinformatics include the use of protein structures for Virtual Screening models such as Quantitative
Structure-Activity Relationship models and proteochemometric models (PCM). Furthermore, a protein's crystal structure can be
used in simulation of for example ligand-binding studies and in silico mutagenesis studies.
Network and systems biology
Network analysis seeks to understand the relationships within biological networks such as metabolic or protein–protein
interaction networks. Although biological networks can be constructed from a single type of molecule or entity (such as genes),
network biology often attempts to integrate many different data types, such as proteins, small molecules, gene expression data,
and others, which are all connected physically, functionally, or both.
Systems biology involves the use of computer simulations of cellular subsystems (such as the networks of metabolites and
enzymes that comprise metabolism, signal transduction pathways and gene regulatory networks) to both analyze and visualize the
complex connections of these cellular processes. Artificial life or virtual evolution attempts to understand evolutionary processes
via the computer simulation of simple (artificial) life forms.
Biodiversity informatics
Biodiversity informatics deals with the collection and analysis of biodiversity data, such as taxonomic databases, or microbiome
data. Examples of such analyses include phylogenetics, niche modelling, species richness mapping, DNA barcoding, or species
identification tools.
The OBO Foundry was an effort to standardise certain ontologies. One of the most widespread is the Gene ontology which
describes gene function. There are also ontologies which describe phenotypes.
Databases
Databases are essential for bioinformatics research and applications. Many databases exist, covering various information types:
for example, DNA and protein sequences, molecular structures, phenotypes and biodiversity. Databases may contain empirical
data (obtained directly from experiments), predicted data (obtained from analysis), or, most commonly, both. They may be
specific to a particular organism, pathway or molecule of interest. Alternatively, they can incorporate data compiled from multiple
other databases. These databases vary in their format, access mechanism, and whether they are public or not.
Some of the most commonly used databases are listed below. For a more comprehensive list, please check the link at the
beginning of the subsection.
The range of open-source software packages includes titles such as Bioconductor, BioPerl, Biopython, BioJava, BioJS, BioRuby,
Bioclipse, EMBOSS, .NET Bio, Orange with its bioinformatics add-on, Apache Taverna, UGENE and GenoCAD. To maintain
this tradition and create further opportunities, the non-profit Open Bioinformatics Foundation[38] have supported the annual
Bioinformatics Open Source Conference (BOSC) since 2000.[39]
An alternative method to build public bioinformatics databases is to use the MediaWiki engine with the WikiOpener (https://ww
w.mediawiki.org/wiki/Extension:WikiOpener) extension. This system allows the database to be accessed and updated by all
experts in the field.[40]
Basic bioinformatics services are classified by the EBI into three categories: SSS (Sequence Search Services), MSA (Multiple
Sequence Alignment), and BSA (Biological Sequence Analysis).[41] The availability of these service-oriented bioinformatics
resources demonstrate the applicability of web-based bioinformatics solutions, and range from a collection of standalone tools
with a common data format under a single, standalone or web-based interface, to integrative, distributed and extensible
bioinformatics workflow management systems.
provide an easy-to-use environment for individual application scientists themselves to create their own workflows,
provide interactive tools for the scientists enabling them to execute their workflows and view their results in real-
time,
simplify the process of sharing and reusing workflows between the scientists, and
enable scientists to track the provenance of the workflow execution results and the workflow creation steps.
Some of the platforms giving this service: Galaxy, Kepler, Taverna, UGENE, Anduril, HIVE.
BioCompute and BioCompute Objects
In 2014, the US Food and Drug Administration sponsored a conference held at the National Institutes of Health Bethesda Campus
to discuss reproducibility in bioinformatics.[42] Over the next three years, a consortium of stakeholders met regularly to discuss
what would become BioCompute paradigm.[43] These stakeholders included representatives from government, industry, and
academic entities. Session leaders represented numerous branches of the FDA and NIH Institutes and Centers, non-profit entities
including the Human Variome Project and the European Federation for Medical Informatics, and research institutions including
Stanford, the New York Genome Center, and the George Washington University.
It was decided that the BioCompute paradigm would be in the form of digital ‘lab notebooks’ which allow for the reproducibility,
replication, review, and reuse, of bioinformatics protocols. This was proposed to enable greater continuity within a research group
over the course of normal personnel flux while furthering the exchange of ideas between groups. The US FDA funded this work
so that information on pipelines would be more transparent and accessible to their regulatory staff.[44]
In 2016, the group reconvened at the NIH in Bethesda and discussed the potential for a BioCompute Object, an instance of the
BioCompute paradigm. This work was copied as both a “standard trial use” document and a preprint paper uploaded to bioRxiv.
The BioCompute object allows for the JSON-ized record to be shared among employees, collaborators, and regulators.[45][46]
Education platforms
Software platforms designed to teach bioinformatics concepts and methods include Rosalind and online courses offered through
the Swiss Institute of Bioinformatics Training Portal. The Canadian Bioinformatics Workshops provides videos and slides from
training workshops on their website under a Creative Commons license. The 4273π project or 4273pi project[47] also offers open
source educational materials for free. The course runs on low cost Raspberry Pi computers and has been used to teach adults and
school pupils.[48][49] 4273π is actively developed by a consortium of academics and research staff who have run research level
bioinformatics using Raspberry Pi computers and the 4273π operating system.[50][51]
MOOC platforms also provide online certifications in bioinformatics and related disciplines, including Coursera's Bioinformatics
Specialization (UC San Diego) and Genomic Data Science Specialization (Johns Hopkins) as well as EdX's Data Analysis for
Life Sciences XSeries (Harvard). University of Southern California offers a Masters In Translational Bioinformatics (http://dtg.us
c.edu/site/index.php/bioinformatics/) focusing on biomedical applications.
Conferences
There are several large conferences that are concerned with bioinformatics. Some of the most notable examples are Intelligent
Systems for Molecular Biology (ISMB), European Conference on Computational Biology (ECCB), and Research in
Computational Molecular Biology (RECOMB).
See also
Biodiversity informatics
Bioinformatics companies
Computational biology
Computational biomodeling
Computational genomics
Functional genomics
Health informatics
International Society for Computational Biology
Jumping library
List of bioinformatics institutions
List of open-source bioinformatics software
List of bioinformatics journals
Metabolomics
Nucleic acid sequence
Phylogenetics
Proteomics
Gene Disease Database
References
1. Lesk, A. M. (26 July 2013). "Bioinformatics" (https://www.britannica.com/science/bioinformatics). Encyclopaedia
Britannica. Retrieved 17 April 2017.
2. Sim, A. Y. L.; Minary, P.; Levitt, M. (2012). "Modeling nucleic acids" (https://www.ncbi.nlm.nih.gov/pmc/articles/PM
C4028509). Current Opinion in Structural Biology. 22 (3): 273–278. doi:10.1016/j.sbi.2012.03.012 (https://doi.org/
10.1016%2Fj.sbi.2012.03.012). PMC 4028509 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028509).
PMID 22538125 (https://www.ncbi.nlm.nih.gov/pubmed/22538125).
3. Dawson, W. K.; Maciejczyk, M.; Jankowska, E. J.; Bujnicki, J. M. (2016). "Coarse-grained modeling of RNA 3D
structure". Methods. 103: 138–156. doi:10.1016/j.ymeth.2016.04.026 (https://doi.org/10.1016%2Fj.ymeth.2016.0
4.026). PMID 27125734 (https://www.ncbi.nlm.nih.gov/pubmed/27125734).
4. Kmiecik, S.; Gront, D.; Kolinski, M.; Wieteska, L.; Dawid, A. E.; Kolinski, A. (2016). "Coarse-Grained Protein
Models and Their Applications". Chemical Reviews. 116 (14): 7898–936. doi:10.1021/acs.chemrev.6b00163 (http
s://doi.org/10.1021%2Facs.chemrev.6b00163). PMID 27333362 (https://www.ncbi.nlm.nih.gov/pubmed/2733336
2).
5. Wong, K. C. (2016). Computational Biology and Bioinformatics: Gene Regulation. CRC Press/Taylor & Francis
Group. ISBN 9781498724975.
6. Joyce, A. P.; Zhang, C.; Bradley, P.; Havranek, J. J. (2015). "Structure-based modeling of protein: DNA
specificity" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366589). Briefings in Functional Genomics. 14 (1):
39–49. doi:10.1093/bfgp/elu044 (https://doi.org/10.1093%2Fbfgp%2Felu044). PMC 4366589 (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC4366589). PMID 25414269 (https://www.ncbi.nlm.nih.gov/pubmed/25414269).
7. Spiga, E.; Degiacomi, M. T.; Dal Peraro, M. (2014). "New Strategies for Integrative Dynamic Modeling of
Macromolecular Assembly". In Karabencheva-Christova, T. (ed.). Biomolecular Modelling and Simulations.
Advances in Protein Chemistry and Structural Biology. 96. Academic Press. pp. 77–111.
doi:10.1016/bs.apcsb.2014.06.008 (https://doi.org/10.1016%2Fbs.apcsb.2014.06.008). ISBN 9780128000137.
PMID 25443955 (https://www.ncbi.nlm.nih.gov/pubmed/25443955).
8. Ciemny, Maciej; Kurcinski, Mateusz; Kamel, Karol; Kolinski, Andrzej; Alam, Nawsad; Schueler-Furman, Ora;
Kmiecik, Sebastian (4 May 2018). "Protein–peptide docking: opportunities and challenges". Drug Discovery
Today. 23 (8): 1530–1537. doi:10.1016/j.drudis.2018.05.006 (https://doi.org/10.1016%2Fj.drudis.2018.05.006).
ISSN 1359-6446 (https://www.worldcat.org/issn/1359-6446). PMID 29733895 (https://www.ncbi.nlm.nih.gov/pubm
ed/29733895).
9. Hogeweg P (2011). Searls, David B. (ed.). "The Roots of Bioinformatics in Theoretical Biology" (https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3068925). PLoS Computational Biology. 7 (3): e1002021.
Bibcode:2011PLSCB...7E2021H (https://ui.adsabs.harvard.edu/abs/2011PLSCB...7E2021H).
doi:10.1371/journal.pcbi.1002021 (https://doi.org/10.1371%2Fjournal.pcbi.1002021). PMC 3068925 (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC3068925). PMID 21483479 (https://www.ncbi.nlm.nih.gov/pubmed/21483479).
10. Hesper B, Hogeweg P (1970). "Bioinformatica: een werkconcept". 1 (6). Kameleon: 28–29.
11. Hogeweg P (1978). "Simulating the growth of cellular forms". Simulation. 31 (3): 90–96.
doi:10.1177/003754977803100305 (https://doi.org/10.1177%2F003754977803100305).
12. Moody, Glyn (2004). Digital Code of Life: How Bioinformatics is Revolutionizing Science, Medicine, and Business
(https://archive.org/details/digitalcodeoflif0000mood). ISBN 978-0-471-32788-2.
13. Dayhoff, M.O. (1966) Atlas of protein sequence and structure. National Biomedical Research Foundation, 215
pp.
14. Eck RV, Dayhoff MO (1966). "Evolution of the structure of ferredoxin based on living relics of primitive amino Acid
sequences". Science. 152 (3720): 363–6. Bibcode:1966Sci...152..363E (https://ui.adsabs.harvard.edu/abs/1966S
ci...152..363E). doi:10.1126/science.152.3720.363 (https://doi.org/10.1126%2Fscience.152.3720.363).
PMID 17775169 (https://www.ncbi.nlm.nih.gov/pubmed/17775169).
15. Johnson G, Wu TT (January 2000). "Kabat Database and its applications: 30 years after the first variability plot"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102431). Nucleic Acids Res. 28 (1): 214–218.
doi:10.1093/nar/28.1.214 (https://doi.org/10.1093%2Fnar%2F28.1.214). PMC 102431 (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC102431). PMID 10592229 (https://www.ncbi.nlm.nih.gov/pubmed/10592229).
16. Attwood TK, Gisel A, Eriksson NE, Bongcam-Rudloff E (2011). "Concepts, Historical Milestones and the Central
Place of Bioinformatics in Modern Biology: A European Perspective" (http://www.intechopen.com/articles/show/titl
e/concepts-historical-milestones-and-the-central-place-of-bioinformatics-in-modern-biology-a-european-).
Bioinformatics - Trends and Methodologies. Bioinformatics – Trends and Methodologies. InTech.
doi:10.5772/23535 (https://doi.org/10.5772%2F23535). ISBN 978-953-307-282-1. Retrieved 8 January 2012.
17. Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR, Fiddes CA, Hutchison CA, Slocombe PM, Smith M
(February 1977). "Nucleotide sequence of bacteriophage phi X174 DNA". Nature. 265 (5596): 687–95.
Bibcode:1977Natur.265..687S (https://ui.adsabs.harvard.edu/abs/1977Natur.265..687S). doi:10.1038/265687a0
(https://doi.org/10.1038%2F265687a0). PMID 870828 (https://www.ncbi.nlm.nih.gov/pubmed/870828).
18. Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL (January 2008). "GenBank" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC2238942). Nucleic Acids Res. 36 (Database issue): D25–30.
doi:10.1093/nar/gkm929 (https://doi.org/10.1093%2Fnar%2Fgkm929). PMC 2238942 (https://www.ncbi.nlm.nih.g
ov/pmc/articles/PMC2238942). PMID 18073190 (https://www.ncbi.nlm.nih.gov/pubmed/18073190).
19. Fleischmann RD, Adams MD, White O, Clayton RA, Kirkness EF, Kerlavage AR, Bult CJ, Tomb JF, Dougherty
BA, Merrick JM (July 1995). "Whole-genome random sequencing and assembly of Haemophilus influenzae Rd".
Science. 269 (5223): 496–512. Bibcode:1995Sci...269..496F (https://ui.adsabs.harvard.edu/abs/1995Sci...269..4
96F). doi:10.1126/science.7542800 (https://doi.org/10.1126%2Fscience.7542800). PMID 7542800 (https://www.n
cbi.nlm.nih.gov/pubmed/7542800).
20. Carvajal-Rodríguez A (2012). "Simulation of Genes and Genomes Forward in Time" (https://www.ncbi.nlm.nih.go
v/pmc/articles/PMC2851118). Current Genomics. 11 (1): 58–61. doi:10.2174/138920210790218007 (https://doi.o
rg/10.2174%2F138920210790218007). PMC 2851118 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2851118).
PMID 20808525 (https://www.ncbi.nlm.nih.gov/pubmed/20808525).
21. Brown, TA (2002). "Mutation, Repair and Recombination". Genomes (2nd ed.). Manchester (UK): Oxford.
22. Carter, N. P.; Fiegler, H.; Piper, J. (2002). "Comparative analysis of comparative genomic hybridization microarray
technologies: Report of a workshop sponsored by the Wellcome trust". Cytometry Part A. 49 (2): 43–8.
doi:10.1002/cyto.10153 (https://doi.org/10.1002%2Fcyto.10153). PMID 12357458 (https://www.ncbi.nlm.nih.gov/p
ubmed/12357458).
23. Chaudhari Narendrakumar M., Kumar Gupta Vinod, Dutta Chitra (2016). "BPGA-an ultra-fast pan-genome
analysis pipeline" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829868). Scientific Reports. 6: 24373.
Bibcode:2016NatSR...624373C (https://ui.adsabs.harvard.edu/abs/2016NatSR...624373C).
doi:10.1038/srep24373 (https://doi.org/10.1038%2Fsrep24373). PMC 4829868 (https://www.ncbi.nlm.nih.gov/pm
c/articles/PMC4829868). PMID 27071527 (https://www.ncbi.nlm.nih.gov/pubmed/27071527).
24. Aston KI (2014). "Genetic susceptibility to male infertility: News from genome-wide association studies".
Andrology. 2 (3): 315–21. doi:10.1111/j.2047-2927.2014.00188.x (https://doi.org/10.1111%2Fj.2047-2927.2014.0
0188.x). PMID 24574159 (https://www.ncbi.nlm.nih.gov/pubmed/24574159).
25. Véron A, Blein S, Cox DG (2014). "Genome-wide association studies and the clinic: A focus on breast cancer".
Biomarkers in Medicine. 8 (2): 287–96. doi:10.2217/bmm.13.121 (https://doi.org/10.2217%2Fbmm.13.121).
PMID 24521025 (https://www.ncbi.nlm.nih.gov/pubmed/24521025).
26. Tosto G, Reitz C (2013). "Genome-wide association studies in Alzheimer's disease: A review" (https://www.ncbi.n
lm.nih.gov/pmc/articles/PMC3809844). Current Neurology and Neuroscience Reports. 13 (10): 381.
doi:10.1007/s11910-013-0381-0 (https://doi.org/10.1007%2Fs11910-013-0381-0). PMC 3809844 (https://www.nc
bi.nlm.nih.gov/pmc/articles/PMC3809844). PMID 23954969 (https://www.ncbi.nlm.nih.gov/pubmed/23954969).
27. Londin E, Yadav P, Surrey S, Kricka LJ, Fortina P (2013). Use of Linkage Analysis, Genome-Wide Association
Studies, and Next-Generation Sequencing in the Identification of Disease-Causing Mutations.
Pharmacogenomics. Methods in Molecular Biology. 1015. pp. 127–46. doi:10.1007/978-1-62703-435-7_8 (https://
doi.org/10.1007%2F978-1-62703-435-7_8). ISBN 978-1-62703-434-0. PMID 23824853 (https://www.ncbi.nlm.ni
h.gov/pubmed/23824853).
28. Hindorff, L.A.; et al. (2009). "Potential etiologic and functional implications of genome-wide association loci for
human diseases and traits" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687147). Proc. Natl. Acad. Sci.
USA. 106 (23): 9362–9367. Bibcode:2009PNAS..106.9362H (https://ui.adsabs.harvard.edu/abs/2009PNAS..106.
9362H). doi:10.1073/pnas.0903103106 (https://doi.org/10.1073%2Fpnas.0903103106). PMC 2687147 (https://w
ww.ncbi.nlm.nih.gov/pmc/articles/PMC2687147). PMID 19474294 (https://www.ncbi.nlm.nih.gov/pubmed/194742
94).
29. Hall, L.O. (2010). Finding the right genes for disease and prognosis prediction. System Science and Engineering
(ICSSE),2010 International Conference. pp. 1–2. doi:10.1109/ICSSE.2010.5551766 (https://doi.org/10.1109%2FI
CSSE.2010.5551766). ISBN 978-1-4244-6472-2.
30. Vazquez, Miguel; Torre, Victor de la; Valencia, Alfonso (27 December 2012). "Chapter 14: Cancer Genome
Analysis" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531315). PLOS Computational Biology. 8 (12):
e1002824. Bibcode:2012PLSCB...8E2824V (https://ui.adsabs.harvard.edu/abs/2012PLSCB...8E2824V).
doi:10.1371/journal.pcbi.1002824 (https://doi.org/10.1371%2Fjournal.pcbi.1002824). ISSN 1553-7358 (https://ww
w.worldcat.org/issn/1553-7358). PMC 3531315 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531315).
PMID 23300415 (https://www.ncbi.nlm.nih.gov/pubmed/23300415).
31. Hye-Jung, E.C.; Jaswinder, K.; Martin, K.; Samuel, A.A; Marco, A.M (2014). "Second-Generation Sequencing for
Cancer Genome Analysis". In Dellaire, Graham; Berman, Jason N.; Arceci, Robert J. (eds.). Cancer Genomics.
Boston (US): Academic Press. pp. 13–30. doi:10.1016/B978-0-12-396967-5.00002-5 (https://doi.org/10.1016%2F
B978-0-12-396967-5.00002-5). ISBN 9780123969675.
32. Grau, J.; Ben-Gal, I.; Posch, S.; Grosse, I. (1 July 2006). "VOMBAT: prediction of transcription factor binding sites
using variable order Bayesian trees" (http://www.eng.tau.ac.il/~bengal/VOMBAT.pdf) (PDF). Nucleic Acids
Research. 34 (Web Server): W529–W533. doi:10.1093/nar/gkl212 (https://doi.org/10.1093%2Fnar%2Fgkl212).
PMC 1538886 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1538886). PMID 16845064 (https://www.ncbi.nlm.
nih.gov/pubmed/16845064).
33. "The Human Protein Atlas" (https://www.proteinatlas.org). www.proteinatlas.org. Retrieved 2 October 2017.
34. "The human cell" (https://www.proteinatlas.org/humancell). www.proteinatlas.org. Retrieved 2 October 2017.
35. Thul, Peter J.; Åkesson, Lovisa; Wiking, Mikaela; Mahdessian, Diana; Geladaki, Aikaterini; Blal, Hammou Ait;
Alm, Tove; Asplund, Anna; Björk, Lars (26 May 2017). "A subcellular map of the human proteome". Science. 356
(6340): eaal3321. doi:10.1126/science.aal3321 (https://doi.org/10.1126%2Fscience.aal3321). PMID 28495876 (h
ttps://www.ncbi.nlm.nih.gov/pubmed/28495876).
36. Ay, Ferhat; Noble, William S. (2 September 2015). "Analysis methods for studying the 3D architecture of the
genome" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556012). Genome Biology. 16 (1): 183.
doi:10.1186/s13059-015-0745-7 (https://doi.org/10.1186%2Fs13059-015-0745-7). PMC 4556012 (https://www.nc
bi.nlm.nih.gov/pmc/articles/PMC4556012). PMID 26328929 (https://www.ncbi.nlm.nih.gov/pubmed/26328929).
37. Hoy, JA; Robinson, H; Trent JT, 3rd; Kakar, S; Smagghe, BJ; Hargrove, MS (3 August 2007). "Plant hemoglobins:
a molecular fossil record for the evolution of oxygen transport". Journal of Molecular Biology. 371 (1): 168–79.
doi:10.1016/j.jmb.2007.05.029 (https://doi.org/10.1016%2Fj.jmb.2007.05.029). PMID 17560601 (https://www.ncb
i.nlm.nih.gov/pubmed/17560601).
38. "Open Bioinformatics Foundation: About us" (http://www.open-bio.org/wiki/Main_Page). Official website. Open
Bioinformatics Foundation. Retrieved 10 May 2011.
39. "Open Bioinformatics Foundation: BOSC" (http://www.open-bio.org/wiki/BOSC). Official website. Open
Bioinformatics Foundation. Retrieved 10 May 2011.
40. Brohée, Sylvain; Barriot, Roland; Moreau, Yves (2010). "Biological knowledge bases using Wikis: combining the
flexibility of Wikis with the structure of databases"
(http://bioinformatics.oxfordjournals.org/content/26/17/2210.full). Bioinformatics. 26 (17): 2210–2211.
doi:10.1093/bioinformatics/btq348 (https://doi.org/10.1093%2Fbioinformatics%2Fbtq348). PMID 20591906 (http
s://www.ncbi.nlm.nih.gov/pubmed/20591906). Retrieved 5 May 2015.
41. Nisbet, Robert (14 May 2009). "BIOINFORMATICS" (https://books.google.com/?id=U5np34a5fmQC&pg=PA328&
q=bioinformatics%20service%20categories%20EBI). Handbook of Statistical Analysis and Data Mining
Applications. John Elder IV, Gary Miner. Academic Press. p. 328. ISBN 9780080912035. Retrieved 9 May 2014.
42. Commissioner, Office of the. "Advancing Regulatory Science - Sept. 24-25, 2014 Public Workshop: Next
Generation Sequencing Standards" (https://www.fda.gov/ScienceResearch/SpecialTopics/RegulatoryScience/uc
m389561.htm). www.fda.gov. Retrieved 30 November 2017.
43. Simonyan, Vahan; Goecks, Jeremy; Mazumder, Raja (2017). "Biocompute Objects—A Step towards Evaluation
and Validation of Biomedical Scientific Computations" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510742).
PDA Journal of Pharmaceutical Science and Technology. 71 (2): 136–146. doi:10.5731/pdajpst.2016.006734 (htt
ps://doi.org/10.5731%2Fpdajpst.2016.006734). ISSN 1079-7440 (https://www.worldcat.org/issn/1079-7440).
PMC 5510742 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510742). PMID 27974626 (https://www.ncbi.nlm.
nih.gov/pubmed/27974626).
44. Commissioner, Office of the. "Advancing Regulatory Science - Community-based development of HTS standards
for validating data and computation and encouraging interoperability" (http://www.fda.gov/ScienceResearch/Speci
alTopics/RegulatoryScience/ucm491893.htm). www.fda.gov. Retrieved 30 November 2017.
45. Alterovitz, Gil; Dean, Dennis A.; Goble, Carole; Crusoe, Michael R.; Soiland-Reyes, Stian; Bell, Amanda; Hayes,
Anais; King, Charles Hadley S.; Johanson, Elaine (4 October 2017). "Enabling Precision Medicine via standard
communication of NGS provenance, analysis, and results". bioRxiv 191783 (https://doi.org/10.1101/191783).
46. BioCompute Object (BCO) project is a collaborative and community-driven framework to standardize HTS
computational data. 1. BCO Specification Document: user manual for understanding and creating B. (https://githu
b.com/biocompute-objects/HTS-CSRS), biocompute-objects, 3 September 2017, retrieved 30 November 2017
47. Barker, D; Ferrier, D.E.K.; Holland, P.W; Mitchell, J.B.O; Plaisier, H; Ritchie, M.G; Smart, S.D. (2013). "4273π :
bioinformatics education on low cost ARM hardware" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751261).
BMC Bioinformatics. 14: 243. doi:10.1186/1471-2105-14-243 (https://doi.org/10.1186%2F1471-2105-14-243).
PMC 3751261 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751261). PMID 23937194 (https://www.ncbi.nlm.
nih.gov/pubmed/23937194).
48. Barker, D; Alderson, R.G; McDonagh, J.L; Plaisier, H; Comrie, M.M; Duncan, L; Muirhead, G.T.P; Sweeny, S.D.
(2015). "University-level practical activities in bioinformatics benefit voluntary groups of pupils in the last 2 years
of school". International Journal of STEM Education. 2 (17). doi:10.1186/s40594-015-0030-z (https://doi.org/10.1
186%2Fs40594-015-0030-z).
49. McDonagh, J.L; Barker, D; Alderson, R.G. (2016). "Bringing computational science to the public" (https://www.nc
bi.nlm.nih.gov/pmc/articles/PMC4775721). SpringerPlus. 5 (259): 259. doi:10.1186/s40064-016-1856-7 (https://d
oi.org/10.1186%2Fs40064-016-1856-7). PMC 4775721
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775721). PMID 27006868 (https://www.ncbi.nlm.nih.gov/pubme
d/27006868).
50. Robson, J.F.; Barker, D (2015). "Comparison of the protein-coding gene content of Chlamydia trachomatis and
Protochlamydia amoebophila using a Raspberry Pi computer" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46
04092). BMC Research Notes. 8 (561): 561. doi:10.1186/s13104-015-1476-2 (https://doi.org/10.1186%2Fs13104
-015-1476-2). PMC 4604092 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604092). PMID 26462790 (https://
www.ncbi.nlm.nih.gov/pubmed/26462790).
51. Wregglesworth, K.M; Barker, D (2015). "A comparison of the protein-coding genomes of two green sulphur
bacteria, Chlorobium tepidum TLS and Pelodictyon phaeoclathratiforme BU-1" (https://www.ncbi.nlm.nih.gov/pm
c/articles/PMC4606965). BMC Research Notes. 8 (565): 565. doi:10.1186/s13104-015-1535-8 (https://doi.org/10.
1186%2Fs13104-015-1535-8). PMC 4606965 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606965).
PMID 26467441 (https://www.ncbi.nlm.nih.gov/pubmed/26467441).
Further reading
Sehgal et al. : Structural, phylogenetic and docking studies of D-amino acid oxidase activator(DAOA ), a
candidate schizophrenia gene. Theoretical Biology and Medical Modelling 2013 10 :3.
Raul Isea The Present-Day Meaning Of The Word Bioinformatics (http://gjar.org/publishpaper/vol2issue1/d75r28.
pdf), Global Journal of Advanced Research, 2015
Ilzins, O., Isea, R. and Hoebeke, J. Can Bioinformatics Be Considered as an Experimental Biological Science (htt
p://www.openscienceonline.com/journal/archive2?journalId=705&paperId=2496) 2015
Achuthsankar S Nair Computational Biology & Bioinformatics – A gentle Overview (http://print.achuth.googlepage
s.com/BINFTutorialV5.0CSI07.pdf), Communications of Computer Society of India, January 2007
Aluru, Srinivas, ed. Handbook of Computational Molecular Biology. Chapman & Hall/Crc, 2006. ISBN 1-58488-
406-1 (Chapman & Hall/Crc Computer and Information Science Series)
Baldi, P and Brunak, S, Bioinformatics: The Machine Learning Approach, 2nd edition. MIT Press, 2001. ISBN 0-
262-02506-X
Barnes, M.R. and Gray, I.C., eds., Bioinformatics for Geneticists, first edition. Wiley, 2003. ISBN 0-470-84394-2
Baxevanis, A.D. and Ouellette, B.F.F., eds., Bioinformatics: A Practical Guide to the Analysis of Genes and
Proteins, third edition. Wiley, 2005. ISBN 0-471-47878-4
Baxevanis, A.D., Petsko, G.A., Stein, L.D., and Stormo, G.D., eds., Current Protocols in Bioinformatics. Wiley,
2007. ISBN 0-471-25093-7
Cristianini, N. and Hahn, M. Introduction to Computational Genomics (http://www.computational-genomics.net/),
Cambridge University Press, 2006. (ISBN 9780521671910 |ISBN 0-521-67191-4)
Durbin, R., S. Eddy, A. Krogh and G. Mitchison, Biological sequence analysis. Cambridge University Press, 1998.
ISBN 0-521-62971-3
Gilbert D (2004). "Bioinformatics software resources" (http://bib.oxfordjournals.org/cgi/content/abstract/5/3/300).
Briefings in Bioinformatics. 5 (3): 300–304. doi:10.1093/bib/5.3.300 (https://doi.org/10.1093%2Fbib%2F5.3.300).
PMID 15383216 (https://www.ncbi.nlm.nih.gov/pubmed/15383216).
Keedwell, E., Intelligent Bioinformatics: The Application of Artificial Intelligence Techniques to Bioinformatics
Problems. Wiley, 2005. ISBN 0-470-02175-6
Kohane, et al. Microarrays for an Integrative Genomics. The MIT Press, 2002. ISBN 0-262-11271-X
Lund, O. et al. Immunological Bioinformatics. The MIT Press, 2005. ISBN 0-262-12280-4
Pachter, Lior and Sturmfels, Bernd. "Algebraic Statistics for Computational Biology" Cambridge University Press,
2005. ISBN 0-521-85700-7
Pevzner, Pavel A. Computational Molecular Biology: An Algorithmic Approach The MIT Press, 2000. ISBN 0-262-
16197-4
Soinov, L. Bioinformatics and Pattern Recognition Come Together (http://jprr.org/index.php/jprr/article/view/8/5)
Journal of Pattern Recognition Research (JPRR (http://www.jprr.org)), Vol 1 (1) 2006 p. 37–41
Stevens, Hallam, Life Out of Sequence: A Data-Driven History of Bioinformatics, Chicago: The University of
Chicago Press, 2013, ISBN 9780226080208
Tisdall, James. "Beginning Perl for Bioinformatics" O'Reilly, 2001. ISBN 0-596-00080-4
Catalyzing Inquiry at the Interface of Computing and Biology (2005) CSTB report (http://www.nap.edu/catalog/11
480.html)
Calculating the Secrets of Life: Contributions of the Mathematical Sciences and computing to Molecular Biology
(1995) (http://www.nap.edu/catalog/2121.html)
Foundations of Computational and Systems Biology MIT Course (https://web.archive.org/web/20071222091912/
http://ocw.mit.edu/OcwWeb/Biology/7-91JSpring2004/LectureNotes/index.htm)
Computational Biology: Genomes, Networks, Evolution Free MIT Course (http://compbio.mit.edu/6.047/)
External links
The dictionary definition of bioinformatics at Wiktionary
Learning materials related to Bioinformatics at Wikiversity
Media related to Bioinformatics at Wikimedia Commons
Bioinformatics Resource Portal (SIB) (http://expasy.org)
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