Biomedical Engineering Reference
In-Depth Information
such as small organic molecules, drugs, and proteins. Aptamers are generated by
an in vitro selection process called SELEX (systematic evolution of ligands by ex-
ponential enrichment). In SELEX, a large library of random oligomer sequences of
the same length are tested for binding affinity with a given target ligand. The se-
quences with highest affinity are separated and amplified by PCR and the process is
repeated until the library has been refined into a subset of sequences with the high-
est binding affinity. Thus, aptamers can be generated with a high affinity for either
antibodies or antigens and applied to a microarray for testing. Binding affinities
of aptamers could be in the picomolar range, much higher than many antibodies.
9.6 Bioinformatics
With the possibility of accumulating large amount of data, new systematic ap-
proaches are required to analyze complex interactions between genes and proteins.
To understand the output results from DNA microarrays, for example, one has to
develop sophisticated statistical tools that can help establish the network of infor-
mation involved in the regulatory pathways controlling the activity of living organ-
isms. Looking through standard text files (called flat files) and tools is easy and has
the advantage that no special tools are required. However, standard text files are
less efficient when the data sets get very large (i.e., more than tens and hundreds of
gigabits of file sizes). Designing efficient databases that are optimized for efficiency
and operating in a high volume so that information can be found quickly based on
certain indexes is essential.
Bioinformatics deals with organizing and understanding the biological data
using the power of computational tools so that data analysis and the sharing of
large sets of data are possible. A fundamental task concerns the creation and main-
tenance of databases of biological information that are already available. For ex-
ample, nucleic acid sequences for many genes and amino acid sequences for many
proteins are known. The storage and organization of millions of nucleotides is
complex. Designing a database and developing an interface whereby researchers
can both access existing information and submit new entries is only the beginning.
There are common methodological statistical principles such as hidden Markov
models and Bayesian statistics for designing and applying information systems that
underlie all work in informatics. For further reading on methodical principles and
development of database, refer to [3]. The databases are predominantly govern-
ment-funded such as the National Center for Biotechnology Information (NCBI,
www.ncbi.nih.gov) and are accessible to the public with a typical Internet browser.
The basics of using different search engines can be accessed at the Web site. An
example is to compare a gene or a gene product as given next.
Once a new sequence of DNA is identified, two or more gene sequences can be
compared for similarity to get a measure of their relatedness. This can be used to
group genes into subsets that might give an indication of the function or activity
of the members of these subsets based upon what is known about the proteins en-
coded by the membership of that subset. A comparison also allows taxonomy to be
examined, as well as the drawing of trees of relatedness, and insights can be made
into sequence evolution. One could use a public nucleotide sequence database such
