Biomedical Engineering Reference
In-Depth Information
The new model-based approaches in human life science emerging out of the
systems biology field are so promising that they are expected to induce the next
paradigm shift in modern medicine towards individual-centered health care. Based
on molecular methods, systems medicine will break boundaries deciphering the
complex mechanisms of diseases, accelerate the discovery of new treatments, and
support the evaluation of clinical trials. But systems medicine can also be used to
design new molecular diagnostic tools [
11
-
13
].
2 Molecular Diagnostics as a Driver for Systems Medicine
As life can be regarded similar to a computational process, a biological system
computes the phenotype out of the genomic information given a specific envi-
ronment [
14
]. Following this paradigm the analysis of the molecular basis is one of
the major cornerstones in modern medicine.
The joint effort of sequencing the first human genome had a huge impact on
molecular biology and transformed the whole field. Following the central dogma
of biology, the biological information stored in the DNA is translated via the RNA
into the building of proteins [
15
,
16
]; the metabolites that are found in a given
organ, tissue, or cell are determined by the presence and activity of proteins in the
given context. Technology development for deciphering biological information
has now reached a level that enables the access and measurement of components
on all levels and even beyond striving to analyse the complete set of molecules in
organelles, cells, whole pathways, or even organs to get a comprehensive view of a
biological system. The 'omics' technologies also comprise methods to detect
protein-protein interaction, protein glycosylation, or the phosphorylation status of
a given protein [
17
-
20
]. The development of the 'omics' technologies aims at
precision, throughput, parallelization of processes, speed, miniaturization, as well
as reducing the amount of sample needed for the analysis, but also reduction in
costs for the machines and the price per sample [
21
].
After a decade of research following the publication of the first draft of the
human genome the next elementary milestone in DNA sequencing was reached in
early 2012 when technology developers published that the magical threshold had
been reached to allow the sequencing of a human genome within one day at a price
of 1,000 USD. This 'third generation' sequencing technology opens the gate for
implementation of whole genome sequencing for routine molecular diagnostics in
clinical application [
22
]. Further development of this breakthrough technology
will allow, for example, the detection of single molecules omitting the amplifi-
cation step for the libraries; real-time detection will speed up the analytical process
beyond the recent timeframe giving rise to possibilities such as online sequencing
during surgery, detection of structural variation, mutations and genetic variability,
modifications, epigenetics, and transcription factor analysis. Transcriptomics
reflects the current status in a given tissue or organ of a patient, and it employs the
same technological basis and is additionally striving for sample reduction towards
