Functional assessment of every gene in the
mammalian cell is an on-going challenge. Understanding, not only the function
of each gene in isolation but the complexity of functional networks and
control systems is of particular importance for discovery of novel and valid
drug targets. Answering complex biological questions in this context
necessitates high- throughput gene functional characterization using an array
of genomic, proteomic and in silico- based tools and technologies.
Related glossaries include
Metabolic
engineering,
Phylogenomics Drug
discovery & development
Proteomics
Informatics
Bioinformatics,
Drug discovery & development
informatics
Genomic
informatics
Protein informatics
Technologies
Genomic technologies
PCR,
Genetic Manipulation
& disruption,
Microarrays
Biology
Cell biology,
Chemistry
& biology
Expression
Gene
Definitions,
SNPs
& genetic variations
Nomenclature, particularly of genes in
humans and in
Model
& other Organisms is an increasing challenge as comparing
completed
genomes
becomes increasingly possible. -Omes & omics
age:
The
time period elapsed since an identifiable point in the life cycle of an
organism. (If a developmental stage is specified, the identifiable point would
be the beginning of that stage. Otherwise the identifiable point must be
specified such as planting).
https://www.ebi.ac.uk/ols/ontologies/efo/terms?short_form=EFO_0000246
A
good illustration of the challenges inherent in cross species comparisons.
biochemical
function: My research is concerned with
the three-dimensional structures of proteins and their biochemical functions.
Gregory Petsko, Brandeis University, 2007
http://www.bio.brandeis.edu/faculty01/petsko.html
biological function:
One key problem in this discussion involves
the definition of "biological function". Geneticists, cellular biologists,
structural biologists, bioinformaticians, and biophysical chemists use
this term to mean different things. Some speakers used the word "function"
to refer to the general biochemical activity of the gene produce (e.g.
kinase activity), others referred to the cellular process in which the
gene product is involved, while to others "function" meant an understanding
of the details of the atomic mechanism of catalysis or recognition.
Still others referred to function in the genetic sense of a generalized
phenotype. This lack of consensus in defining what aspect of function
one might learn about from an examination of
protein structure prevented the group from reaching a consensus on the role that large scale
structural
genomics will have in the related area of
functional genomics.
G. T. Montelione and S. Anderson, Report to the National Science Foundation:
Workshop on Structural Genomics - Understanding Proteins Universal to Life"
Advanced Photon Light Source, Argonne Natl. Laboratories, Jan. 23 - 25, 1998
biological function
The Gene Ontology (GO) provides a
framework and set of concepts for describing the functions of gene
products from all organisms. It is specifically designed for
supporting the computational representation of biological systems. A
GO annotation is an association between a specific gene product and
a GO concept, together making a statement pertinent to the function
of that gene. However, the meaning of the term “function” is not as
straightforward as it might seem, and has been discussed at length
in both philosophical and biological circles. Here, I first review
these discussions. I then present an explicit formulation of the
biological model that underlies the GO and annotations, and discuss
how this model relates to the broader debates on the meaning of
biological function.
The Gene Ontology and the Meaning of Biological Function,
Paul D. Thomas
The Gene Ontology Handbook pp 15-24|,
2016
https://link.springer.com/protocol/10.1007/978-1-4939-3743-1_2/fulltext.html
Related terms:
biological process, Gene Ontology
(GO)
Broader term: function
biological process:
A biological objective to which the
gene or
gene
product contributes. Gene Ontology Consortium "Gene Ontology: tool for the
unification of biology Nature Genetics 25: 25-29 May 2000
A biological process is accomplished via one or more ordered assemblies of
molecular functions. Usually there is some temporal aspect to it, although a
process event may be essentially instantaneous. It often involves
transformation, in the sense that something goes into a process and something
different comes out of it. ... A biological process is not equivalent to a
pathway. We are
specifically not capturing or trying to represent any of the dynamics or
dependencies that would be required to describe a pathway. [The semantic
distinction between a biological process and a molecular function can, at times,
be hard to draw, and GO takes a pragmatic, rather than dogmatic, approach: As a
general rule a process must have >1 distinct steps.] Gene Ontology
Consortium General Documentation, 2001 http://www.geneontology.org/doc/GO.doc.html
comparative genomics:
"We believe that the problem of the
genome- phenotype
connection, which,
in a sense, is the central theme of biology, can be solved only through
an experimental program strategically planned on the basis of
comparative-
genomic
results. Much of the biological research of the next few decades is likely
to develop along these lines. E. Koonin et al "The Impact of Comparative
Genomics on our Understanding of Evolution" Cell 101:573-576 June 9, 2000
Insights can be biochemical,
genetic,
metabolic or physiological. The practice of uncovering the functions of human
genes and other DNA
regions by studying their parallels in nonhumans.
Related terms:
biological
process, molecular
function, Gene Ontology Consortium;
Cell
biology cellular components;
Maps
genomic & genetic comparative
genome mapping;
Model & other organisms;
Phylogenomics comparative proteomics, evolutionary genomics,
Narrower terms:
comparative plant genomics, vertebrate comparative genomics
Background on
Comparative Genomic Analysis, NHGRI, 2007
http://www.genome.gov/10005835
Wikipedia
http://en.wikipedia.org/wiki/Comparative_genomics
deductive genomics:
deductive genomics, or large-scale forward genetics, bridges the gap between
sequence and function by providing a function-driven in vivo screen of a highly
orthologous mammalian model genome for medically relevant physiological
functions and drug targets. This approach allows drug discovery to move beyond
the focus on sequence-driven identification of new members of classical
drug-able protein families towards the biology-driven identification of
innovative targets and biological pathways.
Deductive
genomics: a functional approach to identify innovative drug targets in the
post-genome era. Stumm G, Russ A, Nehls M., Am J Pharmacogenomics. 2(4):
263- 271, 2002
function:
The vagueness of the term 'function' when applied to
genes or proteins emerged as a particular problem, as this term is colloquially
used to describe biochemical activities, biological goals and cellular
structure. Gene Ontology Consortium "Gene Ontology: tool for the
unification of biology Nature Genetics 25: 25-29 May 2000
function as conceived by molecular
biologists (in what could be called the “molecular biology
paradigm”) refers to specific, coordinated activities that have the
appearance of having been designed for a purpose. That apparent
purpose is their function. The appearance of design derives from
natural selection, so many biologists now favor the use of the term
“biological program” to avoid connotations of intentional design.
Following this convention, biological programs, when executed,
perform a function; that is, they result in a particular, previously
selected outcome or causal effect. Biological programs are nested
modularly inside other, larger biological programs, so a protein can
be said to have functions at multiple levels. The Gene
Ontology defines the “universe” of possible functions a gene might
have, but it makes no claims about the function of any particular
gene. Those claims are, instead, captured as “GO annotations.” A GO
annotation is a statement about the function of a particular
gene…The Gene Ontology (GO) considers three distinct aspects of how
gene functions can be described: molecular
function, cellular component,
and biological
process.
In this
representation, a gene encodes a gene product, and that gene product
carries out a molecular-level process or activity (molecular
function) in a specific
location relative to the cell (cellular
component), and this
molecular process contributes to a larger biological objective (biological
process) comprised of
multiple molecular-level processes.
The Gene Ontology and the
Meaning of Biological Function,
Paul D. Thomas
The Gene Ontology Handbook pp 15-24|,
2016
https://link.springer.com/protocol/10.1007/978-1-4939-3743-1_2/fulltext.html
Narrower terms:
biological function, gene
function; Proteomics protein function.
Related terms:
Gene Ontology TM
;
Omes & omics
functome, transcriptome
functional
genome annotation: Functional annotation of the genome
is primarily hampered by the lack of a unified transcript index. Current
transcript information still largely consists of anonymous and highly redundant
ESTs. The situation is further complicated by extensive splicing variation and
elusive gene expression. To address these problems, the Ensembl consortium
relies initially on computational prediction, followed by confirmation with EST/
protein alignments... We have found evidence for a large
number of transcriptional units (65,000- 75,000) and performed initial
annotation and classification. The effective study of transcription and protein
function requires the compilation of all available evidence of transcription and
protein homology. FA Wright et. al. A draft annotation and overview of the human
genome, Genome Biology 2(7): 2001
https://www.ncbi.nlm.nih.gov/pubmed/11516338
functional genomics:
The development and application of global (genome- wide or system- wide)
experimental approaches to assess gene function by making use of the information
and reagents provided by
structural genomics [in the original more limited
sense of construction of high- resolution genetic, physical
and transcript
maps of an organism]. It is characterized by high throughput or large- scale
experimental methodologies combined with statistical and computational
analysis of the results. The fundamental strategy is to expand the scope
of biological investigation from studying single
genes or
proteins to studying
all genes or proteins at once in a systematic fashion. Phil Hieter and Mark
Boguski "Functional Genomics: It's All How You Read It" Science 278: 601- 602,
October 24, 1997
Functional genomics aims to discover the
biological function
of particular
genes and to uncover how sets of genes
and their products work together in health and disease. In its broadest
definition, functional genomics encompasses many traditional molecular
genetic and other biological approaches.
Wikipedia
https://en.wikipedia.org/wiki/Functional_genomics
Related terms: biological process, genome function,
molecular function,
Metabolic
profiling networks, pathways, physiological genomics;
Phylogenomics comparative
genomics, homology, phylogenomics,
functional genomics data:
A useful way to tackle noise and
complexity of functional genomics information is to average the data from
many different genes into broad 'omic categories (Jansen & Gerstein
2000. For instance, instead of looking at how the level of expression of
an individual gene changes over a time- course, we can average all the
genes in a functional category (e.g. glycolysis) together. This gives a
more robust answer about the degree to which a functional system changes
over the time- course. Dov Greenbaum, Mark Gerstein et. al. "Interrelating Different Types of
Genomic Data" Dept. of Biochemistry and Molecular Biology, Yale Univ. 2001 http://bioinfo.mbb.yale.edu/e-print/omes-genomeres/text.pdf.
Related terms:
Omes & omics
functional genomics technologies:
Conditional or tissue- specific
gene
expression in
animal
models is a major area of interest. Other
increasingly popular methods of downregulating gene expression, in order to
study function, include
antisense, ribozyme, and
zinc finger
protein (ZFP) approaches. In addition, a limited number of companies have
developed chemical- genetics methods.
Include
gene disruption, gene manipulation,
gene shuffling, gene targeting, gene trapping, knockdowns, knockins, knockouts, mutagenesis,
phage display, positional cloning, Post Translational Gene Silencing PTGS;
RNA
interference RNAi.
Related terms chemical
genetics, chemical genomics
functional homology: Sequence homology
does not necessarily indicate
functional homology. A number of labs are working with yeast and other
non-human organisms to try to determine what the relationship between sequence
and function might be, if there is any.
functional
profiling: Linking genes and proteins to
disease.
gene function:
The lack of a common language for gene functions is … proving to be
a serious problem. E Pennisi "Seeking common language in a Tower of Babel"
Science 286 (5439): 449 Oct. 15 1999
The
nature of gene function was substantially specified by George W. Beadle
and Edward Tatum [19] and Adrian M. Srb and Norman H. Horowitz [20] when
they showed, using
Neurospora
crassa (Ascomycetes) as their experimental organism, that genes
control the synthesis of enzymes, and in particular that each individual
gene is responsible for the synthesis of one single enzyme. This one gene
- one enzyme hypothesis was the culmination of the classical view of the
gene. ... The classical concept of the gene started to break down as soon
as it had been completely formulated. Petter Portin in "The
Origin, Development and Present Status of the Concept of the Gene: A Short
Historical Account of the Discoveries" Univ. of Turku, Finland,
Current Genomics, 2000
http://www.bentham.org/cg/sample/cg1-1/Portin.pdf
Related terms: biological function, function, genome function, molecular function; protein
function Proteomics
genome function:
Efficient interpretation of the functions of
human
genes and other DNA sequences requires that resources and strategies
be developed to enable large- scale investigations across
whole genomes.
A technically challenging first priority is to generate complete sets of full-
length cDNA clones and
sequences for human and
model- organism genes.
Other functional genomics
goals include studies into
gene
expression
and control, creation of mutations that cause loss or alteration of function
in nonhuman organisms, and development of experimental and computational
methods for protein analyses. [Oak Ridge National Lab, Human Genome Management
Information Services, US] http://www.ornl.gov/hgmis/resource/function.html
genome integrity:
Maintaining the integrity of genetic information is fundamental
for the life of a cell and the survival of a species. Cells can encounter DNA
damage as a consequence of normal cellular metabolism or as a result of exposure
to chemical or physical agents. Humpath.com http://www.humpath.com/genome-integrity
Related term:
DNA
repair
hypomorph:
Loss of function. Related term: null mutation
interactions- molecular: Related
terms: Biomolecules biomolecular
interactions; Omes & omics interactome;
Proteomics protein- DNA interactions, protein- protein interactions, protein-
RNA interactions; RNAi: RNA- RNA interactions
knockout mice:
Model & other
organisms
Knockout-mouse
technology is considered an essential and standard technique in
functional
genomics and
target validation.
molecular function:
The biochemical activity including specific
binding to ligands or structures) of a
gene product. This definition also
applied to the capability that a gene product (or gene product complex) carries
as a potential. It describes only what is done without specifying where or when
the event actually occurs. Gene Ontology Consortium "Gene Ontology:
tool for the unification of biology Nature Genetics 25: 25-29 May 2000
There is a potential for semantic confusion between a gene product and its
molecular function, because very often these are described in exactly the same
words. For example, "alcohol dehydrogenase" can describe what you can
put in an Eppendorf tube (gene product) or it can describe the function of this
stuff. There is, however, a formal difference -- a "product" has a
(potentially) many- to- many relationship with a "molecular function."
Gene Ontology Consortium General Documentation, 2001 http://www.geneontology.org/GO.doc.html
Related
terms: biological function, biological process, function, gene function, Gene OntologyTM;
Cell biology cellular component Gene
definitions gene product
OBO
Foundry Ontologies
http://obofoundry.org/
ortholog (orthologue):
That relationship where sequence divergence
follows speciation, that is, where the common ancestor of the two genes
lines in the cenancestor of the taxa from which the two sequences were
obtained … There is a tendency to wish that there could be only one ortholog
in an organism. This is frequently not the case. Walter Fitch “Homology
a personal view on some of the problem” Trends in Genetics 16 (5): 227-231
May 2000
Narrower term:
Phylogenomics
super- orthologs
orthologous:
Homologous sequences in different species that arose from a common ancestral gene during speciation; may or may not be responsible for a similar function.
NCBI Bioinformatics
paralog (paralogue):
That condition where sequence divergence
follows gene duplication. Such genes might descend and diverge while existing
side by side in the same lineage. Walter Fitch “Homology a personal view
on some of the problem” Trends in Genetics 16 (5): 227-231 May 2000
Narrower term:
Phylogenomics
ultra- paralogs
paralogous:
Homologous sequences within a single species that arose by gene
duplication. NCBI Bioinformatics
Related term:
SNPs
& Genetic variations
duplication
positional cloning:
Involves using a
genetic
map
to determine the location of a disease gene. Researchers use such maps to
analyze genetic markers in extended families that
include individuals affected by a heritable disease, and to pinpoint regions of
the genome that are associated with the disease. They then use that information
to isolate the DNA from the region, and to identify and sequence the disease
gene and identify mutations.
A process which, through
gene
mapping techniques,
is able to locate a gene responsible for a disease when little or no information
is known about the biochemical basis of the disease. [NHGRI] cloning requires a
genetic
map with
a large number of markers (especially in the region of interest), and the
use of physical mapping and DNA
sequencing technologies to isolate and
sequence the targeted gene. A disease gene is usually identified from among
candidate genes in the region of interest by showing that affected individuals
carry mutations within that gene.
Positional cloning was incorrectly called "reverse genetics"
early on. Reverse genetics in its purest definition refers to the analysis
of gene function by assaying proteins expressed from gene variants. "[Positional
cloning] is not "reverse" at all, but rather genetics in its purest form,
unadulterated by any influences of biochemistry, cell biology or physiology."
( Francis S Collins "Positional cloning: Let’s not call it reverse anymore"
Nature Genetics. 1: 3-6, 1992)The term "positional cloning" was coined by Francis Collins.
Related terms: functional cloning, positional candidate approach;
Genetic variations and SNPs
candidate
gene approach;
Maps- genomic & genetic
similarity:
The extent to which nucleotide or protein
sequences are related. Similarity between two sequences can be
expressed as percent sequence identity and/or
percent positive substitutions. BLAST Glossary
https://www.ncbi.nlm.nih.gov/books/NBK62051/ Related term:
homology
siRNA Small interfering RNA:
May be useful in assessing
gene function
Related terms:
RNA RNAi,
Post-Transcriptional Gene Silencing
PTGS
xenology (xenologous):
That conditional (horizontal transfer) where the history
of the gene involves an interspecies transfer of genetic material. It does
not include transfer between organelles and the nucleus. It is the
only form of homology in which the history has an episode where the descent
is not from parent to offspring but, rather, from one organism to another
… Gogarten has proposed a special term, synology, for those xenologs that
arise, not by the transfer of a gene between two species, but by a hybridization
of two species. Walter Fitch “Homology a personal view on some of
the problems” Trends in Genetics 16 (5): 227-231 May 2000
https://www.ncbi.nlm.nih.gov/pubmed/10782117
Bibliography
ArrayExpress, European Bioinformatics Institute
https://www.ebi.ac.uk/arrayexpress/ Functional genomics
data repository
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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