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Drug discovery & development term index: Related glossaries include Protein
informatics Protein
Technologies Proteomics, Proteins,
Protein
categories, Protein
Structures
applied proteomics:
Many current applications of proteomics seem to be
focusing on toxicology and drug target identification and target validation. Related terms: Drug
discovery & development, Targets
bottom up proteomics:
a common method to identify proteins and characterize their amino acid sequences
and post-translational
modifications by proteolytic
digestion of
proteins prior to analysis by mass
spectrometry.[1][2] The
major alternative workflow used in high-throughput proteomics is
called top-down
proteomics and
does not use proteolytic digestion. Essentially, bottom-up proteomics is a means
of determining the protein make-up of a given sample of cells, tissues, etc.[3]
Wikipedia acccessed 2018 Aug
28 http://en.wikipedia.org/wiki/Bottom-up_proteomics
computational proteomics: Large- scale generation and analysis of 3D
and 4D protein structural information and the application of structural
knowledge across all life science disciplines. Edward T. Maggio, Kal Ramnarayan
"Recent developments in computational proteomics" Trends in
Biotechnology 19 (7): 266- 272 July 2001
differential
proteomes: Mass
spectrometry-based differential proteomics is a comprehensive analysis of
protein expression that involves comparing distinct proteomes, such as cells,
tissues or cell lines that are normal, diseased or treated. Mayo Clinic
http://www.mayo.edu/research/core-resources/proteomics-core/mass-spectrometry-based-differential-proteomics
differential proteomics: Mass
spectrometry-based differential proteomics is a comprehensive analysis of
protein expression that involves comparing distinct proteomes, such as
cells, tissues or cell lines that are normal, diseased or treated. This
type of analysis works best for defining differences between groups or
treatments and for the initial "discovery" of potential biomarkers. Mayo
Clinic Proteomics Core
https://www.mayo.edu/research/core-resources/proteomics-core/mass-spectrometry-based-differential-proteomics
differential subproteomes: As defined
by relative solubilities, cellular location and narrow-range immobilised pH
gradients. . SJ Cordwell, AS Nouwens, NM Verrills, DJ Basseal, BJ Walsh,
Subproteomics based upon protein cellular location and relative solubilities in
conjunction with composite two-dimensional electrophoresis gels,
Electrophoresis, 21(6): 1094- 103, April 2000
Broader terms: subproteomes, subproteomics
functional proteomics: constitutes
an emerging research area in the proteomic field whose approaches are
addressed towards two major targets: the elucidation of the biological
function of unknown proteins and the definition of cellular mechanisms at
the molecular level. METHODS: The identification of interacting proteins
in stable complexes in vivo is essentially achieved by affinity-based
procedures. The basic idea is to express the protein of interest with a
suitable tag to be used as a bait to fish its specific partners out from a
cellular extract. Individual components within the multi-protein complex
can then be identified by mass spectrometric methodologies. RESULTS AND
CONCLUSIONS: The association of an unknown protein with partners belonging
to a specific protein complex involved in a particular mechanism is
strongly suggestive of the biological function of the protein. Moreover,
the identification of protein partners interacting with a given protein
will lead to the description of cellular mechanisms at the molecular
level. Functional proteomics.
Monti M1, Orrù
S, Pagnozzi
D, Pucci
P. . Clin Chim
Acta. 2005 Jul 24;357(2):140-50.
https://www.sciencedirect.com/science/article/pii/S0009898105001907?via%3Dihub
Is yielding large databases of interacting proteins and extensive
pathways. Maps of these interactions are being scored and deciphered by
novel high throughput technologies. However, traditional methods of
screening have not been very successful in identifying protein- protein
interaction inhibitors.
location
proteomics: Seeks
to provide automated, objective high-resolution descriptions of protein
location patterns within cells. Methods have been developed to group
proteins into statistically indistinguishable location patterns using
automated analysis of fluorescence microscope images. ... Preliminary work
suggests the feasibility of expressing each unique pattern as a generative
model that can be incorporated into comprehensive models of cell
behaviour. RF Murphy, Location
proteomics: a systems approach to subcellular location,
Biochem Society Transactions, 33 (Pt 3): 535- 538, June 2005
membrane proteomics: Drug
Targets
microproteomics:
analysis
of protein diversity in small samples.
Mass
Spectrom Rev. 2008 Jul-Aug;27(4):316-30. doi: 10.1002/mas.20161.
Microproteomics:
analysis of protein diversity in small samples. Gutstein
HB, Morris
JS, Annangudi
SP, Sweedler
JV. http://www.ncbi.nlm.nih.gov/pubmed/18271009
molecular
(and cellular) proteomics:
SCOPE OF THE JOURNAL Fundamental studies in biology, including
integrative "omics" studies, that provide mechanistic insights; Novel experimental and computational
technologies; Proteogenomic data integration and analysis
that enable greater understanding of physiology and disease processes; Pathway and network analyses of signaling that
focus on the roles of post-translational modifications; Studies of proteome dynamics and quality
controls, and their roles in disease; Studies of evolutionary processes effecting
proteome dynamics, quality and regulation; Chemical proteomics, including mechanisms of
drug action; Proteomics of the immune system and antigen
presentation/recognition; Microbiome proteomics, host-microbe and
host-pathogen interactions, and their roles in health and disease; Clinical and translational studies of human
diseases; Metabolomics to understand functional
connections between genes, proteins and phenotypes
Scope
note Molecular and Cellular Proteomics
http://www.mcponline.org/content/about
Related/equivalent term?: interaction
proteomics
phosphoproteome:
Characterization of post- translational modifications in
proteins is one of the major tasks that is to be accomplished in the post-
genomic era. Phosphorylation is a key reversible modification that regulates
enzymatic activity, subcellular localization, complex formation and degradation
of proteins. DE Kalume et. al,
Tackling
the phosphoproteome: tools and strategies, Current Opinion in Chemical
Biology 7(1): 64- 69, Feb. 2003
Ahn NG, Resing KA (2001) Toward
the phosphoproteome. Nature Biotechnology 19:317- 19318
phosphoproteomics:
Developments in the field of phosphoproteomics have been fueled by the
need simultaneously to monitor many different phosphoproteins within the
signaling networks that coordinate responses to changes in the cellular
environment. Marc Mumby, Deirdre Brekken, Phosphoproteomics: new insights
into cellular signaling, Genome Biology 2005,
6:230 doi:10.1186/gb-2005-6-9-230
physiological proteomics:
Proteomics relying on two- dimensional (2-D) gel
electrophoresis
of proteins followed by spot identification with
mass spectrometry
is an excellent experimental tool for physiological studies opening a new
perspective for understanding overall cell physiology. This is the
intriguing outcome of a method introduced by Klose and O'Farrell
independently 25 years ago. Physiological proteomics requires a 2-D
reference map on which most of the main proteins were identified. ... A
big challenge for future studies is to provide an experimental protocol
covering the fraction of intrinsic membrane
proteins
that almost totally escaped detection by the experimental procedure used
in this study. K. Buttner et. al. A comprehensive two- dimensional map of
cytosolic proteins of Bacillus subtilis Electrophoresis. 22(14):2908-2935,
2001 Aug.
predictive
proteomics:
The search for predictive biomarkers of disease from high-throughput mass
spectrometry (MS) data requires a complex analysis path. Preprocessing and
machine-learning modules are pipelined, starting from raw spectra, to set up a
predictive classifier based on a shortlist of candidate features. As a
machine-learning problem, proteomic profiling on MS data needs caution like the
microarray case. The risk of overfitting and of selection bias effects is
pervasive: not only potential features easily outnumber samples by 103
times, but it is easy to neglect information-leakage effects during
preprocessing from spectra to peaks.
Machine learning methods for predictive proteomics, Annalissa Barla et. Al
Briefings in Bioinformatics
(2008) 9 (2): 119-128.
https://www.ncbi.nlm.nih.gov/pubmed/18310105
quantitative proteomics: Wikipedia http://en.wikipedia.org/wiki/Quantitative_proteomics
regulatory
proteome:
For a
living cell to function in its environment, a large number of regulatory
processes are needed, including regulation of cell proliferation, cell
differentiation and cell death. The underlying mechanisms include
regulation of gene expression, as well as, different post-translational
modifications that control for example activity, stability, localization
or degradation of the protein. An important class of regulatory proteins
are transcription factors that determine when genes are switched on and
off. About 1500 human transcription factors are known and these proteins
are often differentially expressed in different parts of the human body.
Human Protein Atlas
https://www.proteinatlas.org/humanproteome/regulatory
reverse proteomics:
In reverse proteomics, the starting point is the
DNA sequence of the genome of an organism. First, the transcriptome (complete
set of transcripts) and proteome (complete set of proteins) are predicted in
silico and subsequently this information is used to generate reagents for
their analysis. Marc Vidal, AJ Walhout, "Protein Interaction Maps for Model Organisms" Nature
Reviews Molecular Cell Biology 2; 55- 63, Jan. 2001
Compounds can be tested to see if they
can disrupt protein - protein interactions - a strategy that may be extremely
useful for the development of new drugs. Wellcome Trust, UK "The Human
Genome Functional Genomics"
shotgun proteomics:
refers to the use of bottom-up
proteomics techniques
in identifying proteins in
complex mixtures using a combination of high
performance liquid chromatography combined
with mass
spectrometry.[1][2][3][4][5][6] The
name is derived from shotgun
sequencing of DNA which
is itself named after the rapidly expanding, quasi-random firing pattern of a shotgun.
The most common method of shotgun proteomics starts
with the proteins in the mixture being digested and
the resulting peptides are
separated by liquid chromatography. Tandem
mass spectrometry is
then used to identify the peptides.Wikipedia accessed 2018 Aug 28 http://en.wikipedia.org/wiki/Shotgun_proteomics
Instrumentation aside, algorithms for matching
mass spectra to proteins are at the heart of shotgun proteomics. How do
these algorithms work, what can we expect of them and why is it so
difficult to find protein modifications?Shotgun
proteomics is a remarkably powerful technology for identifying proteins,
whether individually or in samples as complex as cell lysates. How do
shotgun proteomics algorithms identify proteins? Edward
M. Marcotte Nature
Biotechnology 25, 755 - 757 (2007) doi:10.1038/nbt0707-755 http://www.nature.com/nbt/journal/v25/n7/full/nbt0707-755.html
structural proteomics: Sometimes referred to as structural genomics, this
discipline involves determining the 3D structures of large numbers of proteins,
ultimately accounting for an organism's entire
proteome. It adds critical
information in at least two points in the
drug discovery pathway: (1) target
identification, or selecting a pathway in which a drug might function, and (2)
medicinal chemistry, or the actual design of compounds to modulate this pathway. A high-throughput, system wide means of determining
gene
function. It
typically involves using high- throughput
X-ray diffraction methods to determine
the structure of proteins encoded by at least one member of each
gene
family in the genome. This approach is coupled with the use of
bioinformatics
as a tool in structural proteomics and computational
modeling
to determine structures of other proteins in the same family. Conversely, an
important goal of structural proteomics is the creation of
databases
of structures. When asked to identify bottlenecks in the structural
proteomics field, several academic and industry scientists pointed to the
need for faster and more reliable protein production and purification
strategies, rather than stronger beams at the X-ray crystallization step.
subproteomics: Advances
in the field of proteomics have made it possible to search for differences
in protein expression between AM [alveolar macrophages] and their
precursor monocytes. Proteome features of each cell type provide new clues
into understanding mononuclear phagocyte biology. In-depth analyses using subproteomics and
subcellular proteomics offer additional information by providing greater
protein resolution and detection sensitivity. HM Wu, M Jin, CB Marsh,
Toward functional proteomics of alveolar macrophages, Am J Physiol Lung
Cell Mol Physiol. 288(4): L585- 595, April 2005 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15757951&query_hl=42
Subproteomics, utilising up to 40 two-dimensional gels per sample will
become a powerful tool for near- to- total proteome analysis in the
postgenome era. Furthermore, this new approach can direct biological focus
towards molecules of specific interest within complex cells and thus
simplify efforts in discovery- based proteome research. SJ Cordwell, AS
Nouwens, NM Verrills, DJ Basseal, BJ Walsh, Subproteomics based upon
protein cellular location and relative solubilities in conjunction with
composite two- dimensional electrophoresis gels, Electrophoresis, 21(6):
1094- 103, April 2000 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10786883&query_hl=42
targeted proteomics: Biochemical
approaches to proteomics, particularly using mass
spectrometry
tissue proteomics:
The
concept of tissues appeared more than 200 years ago, since textures and
attendant differences were described within the whole organism components.
Instrumental developments in optics and biochemistry subsequently paved
the way to transition from classical to molecular histology in order to
decipher the molecular contexts associated with physiological or
pathological development or function of a tissue….Most recently, in the
early 21(st) century, mass spectrometry (MS) has progressively become one
of the most valuable tools to analyze biomolecular compounds. Currently,
sampling methods, biochemical procedures, and MS instrumentations allow
scientists to perform "in depth" analysis of the protein content of any
type of tissue of interest. .. Tissue proteomics represents a veritable
field of research and investment activity for modern biomarker discovery
and development for the next decade.
Tissue proteomics for the
next decade? Towards a molecular dimension in histology.
Longuespée R1, Fléron
M, Pottier
C, Quesada-Calvo
F, Meuwis
MA, Baiwir
D, Smargiasso
N, Mazzucchelli
G, De
Pauw-Gillet MC, Delvenne
P, De
Pauw E.
OMICS. 2014
Sep;18(9):539-52. doi: 10.1089/omi.2014.0033. Epub 2014 Aug 8.
top down proteomics:
a
method of protein identification
that uses an ion
trapping mass
spectrometer to
store an isolated protein ion for mass measurement and tandem
mass spectrometry analysis.[1][2] Top-down proteomics is
capable of identifying and quantitating unique proteoforms through the analysis
of intact proteins.[3] The
name is derived from the similar approach to DNA sequencing.[4] Proteins
are typically ionized by electrospray
ionization and
trapped in a Fourier
transform ion cyclotron resonance (Penning
trap)[5], quadrupole
ion trap (Paul
trap) or Orbitrap mass
spectrometer. Fragmentation for
tandem mass spectrometry is accomplished by electron-capture
dissociationor electron-transfer
dissociation.
Effective fractionation is critical for sample handling before
mass-spectrometry-based proteomics. Proteome analysis routinely involves
digesting intact proteins followed by inferred protein identification using mass
spectrometry.[6] Top-down
proteomics interrogates protein structure through measurement of an intact mass
followed by direct ion dissociation in the gas phase.[7]
Wikipedia accessed 2018 Aug 28 http://en.wikipedia.org/wiki/Top-down_proteomics
toponomics:
a discipline in systems
biology,
molecular cell biology, and histology.
[1][2] It
concerns the study of the toponome of
organisms. The toponome is the spatial network code of proteins and other
biomolecules in morphologically intact cells and tissues.[2][3] The
terms toponome and toponomics were introduced by Walter Schubert in 2003[1] based
on observations with imaging
cycler microscopes (ICM).
The term “toponome” is derived from the ancient Greek nouns “topos” (τόπος;
place, position) and “nomos” (νόμος; law). Hence the term toponomics is
descriptive term addressing the fact that the spatial network of biomolecules in
cells follows topological rules enabling coordinated actions.[1] This
spatial organization is directly revealed by imaging cycler microscopy with
parameter- and dimension-unlimited functional resolution. Wikipedia accessed
2018 Jan 26
https://en.wikipedia.org/wiki/Toponomics
Proteomics
resources
Nature “Post-Genomics Gateway” http://www.nature.com/genomics/post-genomics/index.html
UNI-PROT KnowledgeBase keywords
http://www.expasy.org/cgi-bin/keywlist.pl
Swiss
Institute of Bioinformatics, Geneva Switzerland, European Bioinformatics
Institute, Hinxton, UK,
How
to look for other unfamiliar terms
IUPAC definitions are reprinted with the permission of
the International Union of Pure and Applied Chemistry.
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