Biology Reference
In-Depth Information
IN
TRODUCTION: WHY NM
R?
and statistical analysis, along with identi
ed
metabolic changes in cancer versus control,
and proposed pathway perturbations. Other
reviews surveyed various NMR applications
and touched on the importance of sample collec-
tion, storage, and experimental techniques.
6
e
9
Rather than focusing on identifying speci
Nuclear magnetic resonance (NMR) spectros-
copy has evolved quite a long way from the
rst
successful commercial 60 MHz NMR spectrom-
eter to today
s spectrometer systems equipped
with superconducting magnets operating at as
high as 1,000 MHz. Early NMR spectrometers
were capable of only proton detection; current
systems are capable of multinuclei and multidi-
mensional experiments with sensitivity levels
that theNMR founders could only dreamof. Since
the 1980s, NMR spectroscopy has been exten-
sively used to study molecular structures of small
molecules, proteins, RNA, and large protein-
DNA complexes, as well as interactions among
these entities. In recent years, the combination of
improvements in hardware and chemometric
techniques has made NMR a viable technique
for biomarker discovery. NMR is well suited for
mixture analysis and has many desirable attri-
butes for biomarker discovery: nondestructive
sampling, minimal sample preparation, and
simultaneous detection of metabolites with
different physiochemical properties. NMR
'
c
metabolic biomarkers for pre-existing conditions,
metabolome-wide association studies (MWASs)
have recently emerged as a method for discov-
ering disease risk factors based on metabolite
concentrations in large biological sample sets on
the epidemiology scale.
10
The stability of indi-
vidual metabolic phenotypes over several years
has been demonstratedby Bernini et al.
11
Another
study showed that the stable genetic and environ-
mental in
uences accounts for 60% in plasma and
47% in urine of the biological variations inmetab-
olite concentrations detectable by
1
H NMR.
12
There are many challenges at various stages of
the biomarker discovery process. Physiological
in
uid composition such as
gender, age, diet, hormonal status, stress, and
circadian rhythms have all been well examined
by NMR spectroscopy.
13,14
A comprehensive
review of the NMR biomarker literature is
outside the scope of this chapter. Instead, the
focus will be an overview of the methodologies
employed in biomarker discovery using NMR
spectroscopy with an emphasis on high-
resolution liquid-state spectroscopic techniques.
Some knowledge of NMR spectroscopy is
assumed. For the interested readers, an introduc-
tion to the fundamentals of NMR spectroscopy
including experiments and theoretical back-
ground are explained in two excellent topics by
Keeler
15
and Jacobsen.
16
uences
in bio
s
excellent analytical reproducibility, within and
between laboratories, has been well docu-
mented.
1,2
Under the right conditions, NMR
spectra are quantitative and the area of a peak is
directly proportional to the number of corre-
sponding nuclei.
The feasibility of NMR spectroscopy for
biomarker discovery has been demonstrated in
reviews on cancer biomarker discovery,
3
genetic
disorders,
4
and toxicology.
5
Urine and blood as
well as other biological
'
fluids obtainable with
minimal invasive techniques are ideal samples
for biomarker analysis. The use of NMR spectros-
copy for detecting potential cancer molecular
markers
NMR
HARDWARE ADVANCEM
ENT
uids was recently
compiled by Duarte and Gil.
3
The authors pre-
sented a comprehensive listing of research on 15
types of cancer and tabularized information on
sample collection and storage, data preparation,
in human bio
Starting in the 1990s, tremendous hardware
advancements in magnet and probe technologies
have been achieved to address NMR
'
s inherent
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