Bioinformatics and Computational Biology
understand protein function. Techniques avail-
able to predict the structure depend on the level
of similarity to previously determined protein
structures. In homology modeling, for instance,
structural information from a homologous protein
is used as a template to predict the structure of a
protein once the structure of a homologous protein
is known. State of the art in protein prediction is
regularly gauged at the CASP (Critical Assess-
ment of Techniques for Protein Structure Predic-
tion, http://predictioncenter.org/) meeting, where
leading protein structure prediction groups predict
the structure of proteins that are experimentally
verified.
6. Comparative genomics and phylogenetic analysis.
In this field, the main goal is to identify similarities
and differences between sequences in different
organisms, to trace the evolutionary processes that
have occurred in the divergence of the genomes.
In bacteria, the study of many different species
can be used to identify virulence genes (Raskin
et. al. 2006). Sequence analysis commonly relies
on evolutionary information about a gene or gene
family (e.g. sites within a gene that are highly
conserved over time imply a functional importance
of that site). The complexity of genome evolution
poses many exciting challenges to developers of
mathematical models and algorithms, who have
developed novel algorithmic, statistical and
mathematical techniques, ranging from exact,
heuristics, fixed parameter and approximation
algorithms. In particular, the use of probabilis-
tic-based models, such as Markov Chain Monte
Carlo algorithms and Bayesian analysis, has
demonstrated good results.
7. Text mining. The number of published scientific
articles is rapidly increasing, making it difficult
to keep up without using automated approaches
based on text-mining (Scherf et. al. 2005). The
extraction of biological knowledge from unstruc-
tured free text is a highly complex task requiring
knowledge from linguistics, machine learning
and the use of experts in the subject field.
8. Systems biology. The integration of large amounts
of data from complementary methods is a major
issue in bioinformatics. Combining datasets
from many different sources makes it possible
to construct networks of genes and interactions
between genes. Systems biology incorporates

disciplines such as statistics, graph theory and
network analysis. An applied approach to the
methods of systems biology is presented in detail
by Winzeler (2006).
Biological systems are complex and constantly
in a state of flux, making the measurement of these
systems difficult. Data used in bioinformatics today
is inherently noisy and incomplete. The increasing
integration of data from different experiments adds
to this noise. Such datasets require the application of
sophisticated machine learning tools with the ability
to work with such data.
Machine Learning Tools
A complete suite of machine learning tools is freely
available to the researcher. In particular, it is worth
noting the extended use of classification and regres-
sion trees (Breiman, 1984), Bayesian learning, neural
networks (Baldi, 1998), Profile Markov models (Durbin
et. al. 1998), rule-based strategies (Witten, 2005), or
kernel methods (Schölkopf, 2004) in bioinformatics
applications. For the interested reader, the software
Weka (http://www.cs.waikato.ac.nz/ml/weka/, Witten,
2005), provides an extensive collection of machine
learning algorithms for data mining tasks in general,
and in particular bioinformatics. Specifically, imple-
mentations of well-known algorithms such as trees,
Bayes learners, supervised and unsupervised classi-
fiers, statistical and advanced regression, splines and
visualization tools.
Bioinformatics Resources
The explosion of bioinformatics in recent years has
lead to a wealth of databases, prediction tools and utili-
ties and Nucleic Acids Research dedicates an issue to
databases and web servers annually. Online resources
are clustered around the large genome centers such as
the National Center for Biotechnology Information
(NCBI, http://www.ncbi.nlm.nih.gov/) and European
Molecular Biology Laboratory (EMBL, http://www.
embl.org/), which provide a multitude of public data-
bases and services. For a useful overview of available
links see “The Bioinformatics Links Directory” (http://
bioinformatics.ubc.ca/resources/links_directory/, Fox
et. al. 2005) or http://www.cbs.dtu.dk/biolinks/.