GEN Dictionary Top 100 Terms

TERM DEFINITION
3D Cell Culture 3D cell culture is a microenvironment that emulates native tissue. It may incorporate multiple cell
types and supportive elements, such as extracellular matrix components, but most essentially, it
permits growth in all directions, unlike conventional 2D culture. 3D cell culture may take advantage
of scaffolds, which may be solid or gel-based, to support the growth of spheroids, which are self-
aggregating cell clusters. Absent scaffolding, spheroids may form in hanging drops. 3D cell culture
methods may also involve bioreactors or microfluidic systems to model tissue conditions more
realistically.

3D Printing/ 3D bioprinting is the layer-by-layer deposition of bioink (a mixture of gelling agents, viable cells, and
Bioprinting growth and differentiation factors) to create artificial tissues. Bioinks may be emitted by inkjet,
microextrusion, or laser-assisted devices. In the long-term, 3D bioprinting aims to build complete
organs suitable for transplantation. Currently, 3D bioprinted transplantation material is mostly
limited to thin sheets of skin and cartilage. Of greater sophistication are the various organoids, or
mini-tissues, that have been developed for research and drug-testing purposes.

ADME/Tox ADME/Tox tests are carried out in preclinical and clinical studies to assess the pharmacokinetics
(including the absorption, distribution, metabolism, excretion, and toxicological attributes) of a drug
or compound being developed for therapeutic applications. Given that the cost of developing a new
drug has been pegged at $2.6 billion and that new drugs in Phase I and II trials fail in the range of
35% to 57%, ADME/Tox studies are critical to new product development.

Animal Models Animal models are nonhuman species that serve as proxies for humans in studies of development
and disease, as well as in drug testing. The advantages of animal models include the convenience of
brief life spans and the freedom with which genetic manipulation may be exercised. Disadvantages
include genetic, metabolic, and physiological differences between model species and humans that
could confound biomedical research. Bioethical concerns are also being extended to nonhuman
species, therefore alternatives to animal models, such as “body on a chip” systems, are being
investigated.

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Antibody An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced by the body's
immune system when it detects antigens. Antibodies are used by the immune system to identify and
neutralize pathogens such as bacteria and viruses. Antibodies are utilized by many researchers in
protein and small-molecule detection and isolation applications, from Western blotting to enzyme-
linked immunosorbent assay (ELISA) to immunoprecipitation. They are also used to purify and detect
proteins and to identify cellular structures using immunofluorescence.

Assay An assay is a laboratory procedure whereby the amount or the binding activity of a substance is
determined. In the life sciences, the substance, or analyte, is usually a drug or biological molecule,
such as an enzyme, that is part of a sample that contains a great many constituents, many of which
are hard to distinguish from the substance of interest. Hence, assay signals (such as
spectrophotometer readings, gel stains, or rates of reagent consumption) may be accompanied by
considerable noise. To boost signals, assays may be accompanied by separation or amplification
procedures.

Biobanking Biobanking is the archiving of biological specimens, such as blood, plasma, skin cells, and organ
tissue. Biobanks preserve specimens, often through the use of cryogenics, until they are needed by
medical researchers, who may withdraw specimens on the basis of criteria, such as donor age,
gender, ethnicity, or exposure to environmental influences. Biobanks are particularly valuable in
genomics research and the identification of disease biomarkers. Biobanking operations are
concerned with observing practices, such as informed consent, data disclosure, and sample de-
identification, to comply with bioethics guidelines.

Bioinformatics Bioinformatics is the application of computer technology to the organization, analysis, and
interpretation of biological data, particularly genomic data. For example, bioinformatics may be used
to analyze DNA sequences and isolate disease-associated gene variants, or even map connections
between molecular conspirators in intricate disease processes. The search for connections may be
sought at just one informational level, the level of the genome, for example, or it may survey other
levels, such as the transcriptome and the metabolome. Bioinformatics may also extend to molecular
phylogenetic, cheminformatic, and protein structure/function dimensions.

Biologic A biologic is a product, such as a recombinant protein or a vaccine, that is made in microorganisms,
plants, or animal cells for therapeutic applications. Drugs, on the other hand, are manufactured via
chemical synthesis. Process control in biologics manufacturing is especially demanding because even
a seemingly minor process change can impact the bacterial, mammalian, plant, or insect host system
that makes the biologic so that both the structure and function of the final product are not what was
originally expected.

Biomarker Biomarkers are substances, structures, or processes that can be measured in the body or its
products and are valued as accurate and reproducible indicators of some biological state or
condition. They are often measured and evaluated to examine normal biological processes,
pathogenic processes, or pharmacologic responses to a therapeutic intervention.

Bioprocess Bioprocess scale-up is a series of actions whereby data from laboratory studies is used for the
Scale-Up production of a biologic in a small pilot plant to assess product characteristics and process
performance. The information gained from the pilot plant study is evaluated to determine if the
product should proceed to manufacture on the commercial scale, the final scale-up step. Both
stainless-steel and single-use bioreactors/fermenters can be employed at the pilot plant and large-
scale manufacturing stages.
Bioreactors/ Bioreactors are vessels, either stainless steel or single use, where a number of different types of
Fermenters aerobic or anaerobic microorganisms as well as animal and plant cells are cultured for the
production of therapeutic proteins. Fermenters, on the other hand, operate as closed anaerobic
vessels producing biotherapeutic products via the activity of prokaryotic microorganisms.

Biosimilar A biosimilar is an FDA-approved biological product that has been shown to be very similar to a
previous FDA-approved therapeutic, which is known as the reference product. Biosimilars exhibit the
same basic safety and effectiveness characteristics as the reference product. The FDA requires that
only minor differences in clinically inactive components of a biosimilar are permissible in that
product.

Cell Culture Cell culture is the removal of cells from multicellular organisms and the growth and maintenance of
these cells in artificial media. Primary cells, which are taken directly from living donors, tend to
produce cultures with limited lifespans. Exceptions include cell cultures derived from tumor samples.
Through adventitious mutation or deliberate manipulation, including genetic engineering, cells may
acquire the ability to proliferate indefinitely. Such cells, said to be immortalized, may give rise to
established cell lines. Cell culture technology encompasses media formulation, environmental
control, and choice of adherent or suspension formats, as well as 2D/3D options. Cell culture is
fundamental to biomedical research, drug development, and tissue engineering.

Cell Culture A cell culture medium, whether it is serum free or composed of animal serum, is used to support the
Medium growth of bacterial, mammalian, plant, or insect cells. In recent years the biomanufacturing industry
has favored serum-free cell culture media to avoid possible contamination from adventitious and
infectious agents associated with the use of animal-derived sera.

Cell-Line Cell-line development is a biomanufacturing procedure in which a cell line [such as Escherichia coli
Development and Chinese hamster ovary (CHO) cells] is developed primarily for its ability to deliver high product
yields. The cell line must also be able to grow and function within the parameters of a specific
production system. Regulatory authorities require that cell lines be developed, cloned, and
characterized according to strict guidelines.

Cell Signaling Cell signaling refers to the processing of mechanical signals (forces that are exerted on or by the cell)
and chemical signals (ions or molecules that are transmitted and received within the cell, or
transmitted outside the cell and received by the same cell, nearby cells, or distant cells). In
multicellular organisms, signaling molecules include hormones, neurotransmitters, and cytokines.
(Signals may be passed between organisms, too.) External signals may trigger intracellular
sequences, i.e., signal transduction pathways, to bring about environmental responses. Proper cell
signaling is needed to maintain homeostasis, drive development, and coordinate defense or repair.
Aberrant cell signaling can give rise to diseases such as cancer.

Cell-Based Cell-based assays use cultured cells, including cells from immortalized cell lines, primary cell lines,
Assay and stem cell lines, to represent the response of native tissues or model organisms to different
circumstances, such as exposure to a drug. Cell-based assays may measure cell proliferation and
death, motility and morphology, ligand-receptor binding and signal transduction, and gene
expression and other cell activities. Demand for certain cell-based assays, such as assays that can
predict toxic responses to drugs, is driving advances in automation and high-throughput screening.
Chem-Seq Chem-seq, a technique that combines chemical affinity capture and massively parallel DNA
sequencing, is used to map the genomic sites targeted by small molecules. The technique is related
to ChIP-seq, which localizes genome-wide DNA–protein interactions, in that small molecules of
interest are modified to carry a biotin moiety, which is then subjected to cross-linking, similar to the
way DNA-binding proteins are treated in ChIP-seq. Once the protein cross-links are fixed, chromatin
may be fragmented, and DNA segments and their biotinylated attachments may be precipitated.
Unlike ChIP-seq, which relies on antibodies for the precipitation step, Chem-seq makes use of small-
molecule affinity probes. Ultimately, DNA segments associated with biotinylated species of interest
are enriched and subjected to next-generation sequencing.

ChIP-Seq ChIP-seq, or chromatin immunoprecipitation sequencing, is a technique for generating genome-wide

maps of DNA–protein binding sites for proteins of interest, such as transcription factors, chromatin-
modifying enzymes, and modified histones that interact with DNA. In ChIP-seq, DNA–protein cross-
links may be fixed so that when chromatin is fragmented, DNA segments co-precipitate with DNA-
binding protein, which is “pulled down” with antibodies. Ultimately, these DNA segments are
analyzed by means of microarrays or next-generation sequencing.

Chromatogra- Chromatography refers to different types of techniques that are used to separate and identify
phy complex mixtures of biological or chemical materials on a column. The material that moves through
the column is the mobile phase and the substance fixed to the column is the stationary phase. The
two main types of chromatography used in life science research are gas chromatography and liquid
chromatography.

Circulating Circulating tumor cells (CTCs) are cells that have been shed into the vasculature from a primary
Tumor Cells tumor and circulate in the bloodstream. It is believed that CTCs constitute seeds for metastases in
(CTCs) distant organs. The detection of CTCs may have important prognostic and therapeutic implications,
but because their numbers can be very small, these cells are not easily detected.

Companion Companion diagnostics (CDx) are medical tests that provide information to ensure the safe and
Diagnostic effective use of a corresponding drug or biological product. These in vitro diagnostics help
(CDx) healthcare professionals determine which patients could be helped by that drug and which patients
would not benefit, or could even be harmed. CDx tests are reviewed and approved by the U.S. FDA.

Complementary Complementary DNA (cDNA) is an intron-free form of DNA that is synthesized from a single-stranded
DNA (cDNA) RNA template, such as a messenger RNA (mRNA). Production of single-stranded cDNA is facilitated
by reverse transcriptase. Double-stranded DNA is produced when the single-stranded cDNA is
relieved of its mRNA partner by an RNase and then is acted upon by DNA polymerase. The cDNA
generated from a cell or tissue sample’s mRNA can be compiled in a cDNA library, giving a gene-
expression profile particular to a given time or set of conditions. In the laboratory, cDNA is often
used to clone eukaryotic genes in prokaryotes; in nature, cDNA is part of a retrovirus-perpetuating
mechanism.

Contract A contract manufacturing organization is a company that carries out biomanufacturing operations
Manufacturing for a fee for multiple clients. Among CMOs are a growing number of Contract Development and
Organization Manufacturing Organizations (CDMOs) that also perform drug development services in addition to
(CMO) biomanufacturing activities. One of the biggest risks that client companies need to manage when
working with a CMO or CDMO is loss of control of their product.
Contract A contract research organization (CRO) is a company that carries out wide range of new drug
Research development activities for a fee for multiple clients. CROs perform drug discovery and development
Organization research, toxicology studies, preclinical work, patient recruitment, pharmacovigilance, and clinical
(CRO) studies, including managing clinical trials. They also provide site monitoring, and offer insights on
regulatory affairs.

CRISPR/Cas9 CRISPR/Cas9 is a prokaryotic immune system that has been adapted for genetic engineering. CRISPR
stands for clustered regularly interspaced short palindromic repeats, which are lengths of DNA that
contain short repeating base patterns. These lengths are interspersed with more meaningful spacer
elements, which are essentially records of previous encounters with viruses or plasmids. Of all the
details of the prokaryotic system, the most important may be the CRISPR-associated protein-9 (Cas9)
nuclease. Actually, this nuclease is particular to Streptococcus pyogenes. While there are analogous
nucleases in other organisms, Cas9 is the nuclease that is most widely used in genetic editing. When
Cas9 is loaded with a guide RNA, it may bind (and cut) complementary stretches of DNA, and so
CRISPR/Cas9 provides a convenient means of knocking out target genes. Elaborated versions of
CRISPR/Cas9 exploit a gene-repair mechanism, homology-directed repair, to accomplish nucleotide
insertions at selected genomic sites. Also, CRISPR/Cas9 has been modified to accomplish other tasks,
such as gene interference and activation.

DNA DNA, or deoxyribonucleic acid, carries most of the genetic instructions used in the growth,
development, functioning, and reproduction of all humans and most organisms. Nearly every cell in
a person’s body has the same DNA. The information in DNA is stored as a code made up of four
chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of
about 3 billion base pairs, more than 99% of which are the same in all people.

DNA Whereas DNA synthesis may be taken to mean either the natural or artificial creation of DNA, gene
Synthesis/ synthesis implies that DNA is being produced artificially. Gene synthesis, the writing rather than the
Gene Synthesis sequencing of DNA, tends to be outsourced to specialist companies, which painstakingly produce
segments that string together about 200 base pairs. Typically, this work uses solid-phase synthesis to
join oligonucleotides without the need for template DNA, unlike molecular cloning or assembly PCR.
Segments may be joined to create longer strands. Even more ambitious is the synthesis of artificial
genomes. Such large-scale work, it has been proposed, will require new methods. One possibility is
multiplex assembly.

Electrophoresis Electrophoresis is a separation technique that makes use of an electric field to force charged
macromolecules, such as proteins and oligonucleotides, through a medium, usually a gel. A
macromolecule’s charge and size affects how easily it moves through the medium, which acts like a
sieve, and the relative distances traveled by different macromolecules in a mixture may be visualized
by various means, including dyes and fluorescent tags.

ELISA ELISA, or enzyme-linked immunosorbent assay, is a technique that makes use of a surface-
immobilized antibody to detect a specific target (such as a protein with antigenic properties) that
originates from a liquid sample. Alternatively, a surface-immobilized antigen may be used to detect a
specific antibody. In a simple example of the antigen-detection case, an antigen of interest is first
bound by a well- or tube-coating “capture” antibody, unbound antigen is washed away, and then the
bound antigen is exposed to a second antibody, one to which an enzyme has been attached. Bound
enzyme may then act on a substrate to produce a signal such as an optically detectable product.
Variations on this basic ELISA technique are readily implemented, as are high-throughput
microarray-based formats.
Epigenetics Epigenetics refers to patterns of gene activity that are not due to genetic code, the DNA nucleotide
sequence, but are rather due to factors such as DNA methylation, histone modification, and
noncoding RNA. These patterns are modified during development, such that terminally
differentiated cells of different types—nerve cells, muscle cells, and so on—assume and maintain
distinct gene-expression profiles. Some diseases are associated with epigenetic variation. Also,
lasting changes to epigenetic patterns may occur due to environmental influences, lifestyle, aging,
and disease. There are indications that some such changes may be heritable.

Exosome An exosome is a more or less spherical vesicle that is shed (or taken up) by a cell, contains fluid, and
is enclosed by a lipid bilayer. An exosome may originate from an intracellular vesicle (endsome), or it
may arise from the cell membrane. They are 30–150 nm across, and they are found in cell cultures
and in biological fluids such as blood, saliva, and urine. Exosomes may ferry molecules such as RNAs
and proteins from one cell to another, traversing extracellular space and enabling a form of
intercellular communication. Exosomes show promise as diagnostic biomarkers and as carriers of
therapeutic cargoes.

Fill and Finish The fill-and-finish stage of biomanufacturing takes place after upstream bioprocessing and
downstream purification. Fill-and-finish services for the final product include prefilled syringes,
cartridges, vials, filling, formulation support, lyophilization, visual inspection, labeling, and
packaging. All of these activities are performed in an aseptic environment because any kind of
contamination at this point in drug development could lead to a failed product and the loss of
millions of dollars in product investment.

Filtration Filtration is a downstream technology that separates a target molecule or product from a complex
mixture of biomaterials that had been produced in an upstream bioreactor or fermenter. Filters are
designed to remove cell debris, discarding particles and bacterial contaminants. Sterile filtration is
used during the formulation and filling process of the finished product.

FISH FISH, or fluorescence in situ hybridization, is a probe-based method for localizing DNA sequences on
chromosomes. Alternatively, it may be used to localize RNA targets in cell preparations and tissue
sections. Probes consist of fluorescently labeled oligonucleotides that hybridize with complementary
sequences of interest. FISH analyses may make use of multiple probes and multiple fluorophores,
and fluorophore detection may be accomplished by means of bright-field or fluorescence
microscopy. The collection of per-cell measurements may be automated by flow cytometry.

Flow Flow cytometry is an automated approach to the analysis of particles, usually cells, in heterogeneous
Cytometry samples. It can, for example, be used to count or sort cells that flow through a narrow liquid stream
and pass, one at a time, past a detector or series of detectors. Cell components may be fluorescently
labeled so that they emit excitation light when they are illuminated by a flow cytometer’s lasers, and
the excitation light, once optically detected, provides a signal that may be processed by the flow
cytometer’s electronics. (Label-free systems, which rely on electrical impedence rather than light
measurement, are also available.) Besides cell counting and sorting, flow cytometers may
simultaneously measure multiple chemical and physical characteristics of individual cells.
Gene Silencing Gene silencing, the inhibition of the expression of one or more genes, is accomplished by cells when
they differentiate, during development, or when they regulate their own behavior. It is also a
mechanism that is used to further drug development and medical research. For example, gene
knockdown, the reduction (but not the elimination of gene expression) may be accomplished in the
laboratory by means of RNA interference (RNAi) or CRISPR interference (CRISPRi). RNAi works at the
translational level by destroying specific mRNA molecules; CRISPRi works at the transcriptional level
through steric inhibition.

Gene Therapy Gene therapy is the modification of genetic material in cells to prevent or treat disease. Selected
genes may be disabled or replaced, or entirely new genes may be introduced. Genetic engineering
components, such as transplantable DNA and retroviral RNA, may be delivered to cells by various
means including viral vectors and electroporation. Gene therapy, still an experimental technique, is
applied only if there is no other attractive treatment, and even then, its clinical use has been limited
to the modification of somatic cells. With the rise of gene-editing technologies that are both
powerful and relatively easy to implement, such as CRISPR/Cas9, many scientists have called for a
moratorium on the modification of germline cells in clinical contexts.

Generics A generic, or bioequivalent, is a kind of drug that is the same as a brand name drug in dosage form,
safety, strength, route of administration, quality, performance characteristics, and intended use.
Instead of filing a New Drug Application (NDA), companies seeking FDA approval to market a generic
drug submit an Amended New Drug Application (ANDA).

Genome Genome editing is the use of nucleases to alter, delete, or add DNA to an organism’s genome.
Editing Nuclease platforms include homing endonucleases, zinc finger nucleases, transcription activator-like
effector nucleases (TALEN), and RNA-guided nuclease systems such as CRISPR/Cas9. Once a nuclease
is used to insert a break at a specific genomic site, one or another repair mechanism—homology
directed repair (HDR) or nonhomologous end joining (NHEJ)—may be favored. Because HDR relies
on a homologous sequence to patch sequences where DNA is missing, it may be supplied with a
nucleotide template so that it inserts a desired sequence. NHEJ is an error-prone process, and so it is
often used to disable selected genes.

Genome-Wide A genome-wide association study (GWAS) is the examination of the entire genome for genetic
Association variants, chiefly single-nucleotide variations (SNPs), associated with particular traits, such as
Study predisposition to certain diseases. GWASs typically involve whole-genome sequencing, the gathering
of genetic information from large numbers of people, and analyses that examine new sequencing
results in the context of reference genome information. GWAS analyses are statistically challenging
because associated variants are not necessarily causal, and multiple variants may contribute to
complex diseases such as cancer. Still, GWAS shows promise in personalized medicine, the point of
which is to customize treatment according to a patient’s unique genomic profile.

Genomics Genomics is the comprehensive study of the DNA in a genome, both the coding and the noncoding
segments. It seeks to clarify how different genomic regions interact to contribute to growth and
development, as well as individuals’ propensities toward health or illness. It relies on techniques
such as DNA sequencing and bioinformatics to map genes and elucidate their functions.
Genotyping Genotyping is the identification of genetic variants associated with the inherited traits of an
individual or population. A search for predetermined variants of interest may be conducted, for
example, with genotyping chips or arrays. Alternatively, a comprehensive search of genomic regions,
or even entire genomes, may be undertaken by means of DNA sequencing, which may reveal
unique, unforeseen variants.

Glycan Analysis Glycan analysis evaluates glycosylation, the process whereby a sugar molecule is attached to a
eukaryotic cell protein. Glycosylation is a critical post-translational modification of that protein in
terms of structure and proper functioning. Proteins that have been glycosylated play key roles in
numerous biological and physiological processes. Glycan analysis may also involve the study of a
protein to insure that it has the proper structure and has been glycosylated correctly. A range of
techniques can be used to carry out glycan analysis, including chemical, enzymatic, mass
spectrometric, and nuclear magnetic resonance.

GPCRs GPCRs, or G-protein-coupled receptors, are large proteins that span the cell membrane. These
proteins, which occur only in eukaryotes, can sense extracellular molecules and activate intracellular
reaction pathways, enabling cellular responses to external stimuli. There are many different GPCRs,
and they bind with different ligands to accomplish myriad functions. Yet GPCRs are alike in
consisting of seven segments that traverse the cell membrane. Also, GPCRs typically undergo shape
changes when they bind with ligands, altering their interactions with intracellular G proteins to
trigger signal cascades, many of which have roles in disease. Accordingly, GPCRs are attractive drug
targets.

High-Content High-content analysis (HCA), or high-content screening (HCS), is a technique used in the life sciences
Analysis to identify substances that alter the phenotype of the medium used for screening (typically cultured
(HCA)/High- cells). This method is designed to provide rapid results and is often referred to as high-throughput
Content phenotypic screening.
Screening
(HCS)

High- High-throughput screening (HTS) is a methodological approach in the life sciences, especially for
Throughput drug discovery, that utilizes technology and equipment, such as robotics, liquid-handling devices,
Screening and automation software, to generate data rapidly from a large number of samples.
(HTS)

Immunoassay An immunoassay is a biochemical test that detects the presence of an analyte through the use of
antibodies. These assays can either be qualitative (such as the lateral flow tests provided in home
pregnancy kits), providing a simple positive or negative result, or quantitative (such as some types of
ELISAs), allowing researchers to calculate the amount of analyte present.

Immuno- Immuno-oncology uses or enhances the patient’s own immune system to stop the growth of cancer
oncology cells. This highly touted therapy has progressed considerably in recent years with approvals for the
use of various immuno-oncology therapies, including vaccines, cytokines, tumor-directed
monoclonal antibodies, and immune checkpoint inhibitors.
Induced Induced pluripotent stem cells (iPSCs) are adult cells that have been reprogrammed to emulate the
Pluripotent pluripotency of embryonic stem cells. Adult cells are reprogrammed by inducing them to incorporate
Stem Cells genes that encode pluripotency-associated transcription factors, or by providing transcription
factors directly. The most commonly transduced genes are Oct4, Sox2, cMyc, and Klf4, and they may
be delivered by various means, including viral vectors. Although iPSCs raise safety issues, not the
least of which is the promotion of cancer, they are of great interest in regenerative medicine. After
directed differentiation, patient-derived iPSCs could be used to generate genetically matching donor
tissue. iPSCs are already useful in research, where they help model disease and screen therapeutics,
and they avoid the ethical concerns raised by embryonic stem cells.

Ion Channels Ion channels are pore-forming transmembrane proteins that regulate the flow of biologically
important ions (e.g., Na2+, K+, or Cl—) across cellular membranes. There are two main features that
distinguish ion channels from other ion transport proteins: first, the rate of transport through the
channel is high (106 ions/sec or greater) and second ions flow through channels down their
electrochemical gradients—a function of ion concentration and membrane potential. Ion channels
can be classified in many different ways: their gating mechanism (e.g., voltage or ligand), by the type
of ion they transport, or their location within the cell, to name a few.

Kinases Kinases constitute a biological important class of enzymes that catalyze the transfer of phosphate
groups (PO4) from high-energy, phosphate donors, e.g., adenosine triphosphate (ATP), to a specific
substrate in a process known as phosphorylation. Phosphatases are the exact opposite of kinases
and remove phosphate groups.

Laboratory Laboratory developed tests (LDTs) are a controversial type of in vitro diagnostic test that is designed,
Developed manufactured, and used within a single laboratory. The FDA wants to regulate these tests as it
Tests (LDTs) believes that as LDTs have become more complex; many LDTs consist of components that are not
legally marketed for clinical use and others are used beyond local populations and manufactured in
high volume. The FDA wants to assign LDTs risk classifications of low, moderate, and high, based on
existing classes of medical devices.

Laboratory A laboratory information management system (LIMS) is software designed to manage laboratory
Information protocols and information, supporting modern laboratory operations. Some key features of LIMS are
Management workflow and data tracking support, flexible architecture, and data exchange interfaces.
System (LIMS)

Liquid Biopsies Liquid biopsies are a less-invasive and more cost-effective liquid sampling methodology for cancer
diagnosis. They are used for any type of specimen other than tissue—including blood, urine, and
cerebrospinal fluid. There are two main types of biomarkers assessed by liquid biopsies: cell‐free
DNA (also known as circulating tumor DNA) and circulating tumor cells.

Liquid Handling Liquid handling refers to automated methods and devices that rapidly and accurately dispense
selected quantities of reagent, samples, or other liquid to a designated container.

Long Long noncoding RNA (lncRNA) constitutes a class of oligonucleotides that are nonprotein coding
Noncoding transcripts. They are typically, and somewhat arbitrarily, distinguished as being longer than 200
RNA (lncRNA) nucleotides in length. lncRNAs are part of a larger group of noncoding RNA (ncRNA) molecules that
are involved in gene regulation through a variety of mechanisms, such as regulating basal
transcription machinery, post-transcriptional regulation (splicing, siRNA), and epigenetic modulation.
Mass Mass spectrometry is a sensitive analytical technique that ionizes chemical compounds and sorts the
Spectrometry ions on the basis of their mass-to-charge ratio. The earliest mass spectrometry devices were used
primarily to qualitatively detect minute amounts of various compounds in a sample; yet over the
years, advances in mass analyzers, detectors, and separation techniques have allowed mass
spectrometry to be used an extremely sensitive and accurate measuring device of various
biomolecules.

Metabolites Metabolites are substances produced during metabolism (digestion or other bodily chemical
processes). They are the intermediate products of metabolic reactions catalyzed by various enzymes
that occur within cells. Primary metabolites, including amino acids, alcohols, vitamins (B2 and B12),
polyols, and organic acids, are synthesized by the cell because they are indispensable for their
growth. Secondary metabolites, including antibiotics, dyes, pigments, and pesticides, are compounds
produced by an organism that are not required for primary metabolic processes.

Microarray A microarray is a two-dimensional, miniaturized high-throughput screening device on a solid support

(glass or silicon thin film) that allows for the concomitant detection of vast amounts of biomolecules.
Microarrays can be used to analyze a variety of molecules—proteins, carbohydrates, antibodies,
RNA, and DNA—with DNA arrays becoming the most popular and widely used over the years. Once
the biomolecule is placed onto the solid support, probes are used to determine of a particular
molecule or genetic sequence is present. Their presence is usually detected and quantified through
the detection by some visual means (fluorescence, chemiluminescence, etc.).

Microbiome The microbiome is the collection of microorganisms and their genetic material within a particular
environment. In recent years, the relationship between humans and their microbiome has been
clarified. Many microorganisms are generally nonpathogenic and exist symbiotically in their hosts.
Also, microbiome studies have provided insight into a vast number of diseases and opened the door
to potential new therapeutics.

Microfluidics Microfluidics is the science dealing with products and services that control the flow of liquids in the
micro to picoliter range through micrometer-sized channels. Systems are typically designed to
increase multiplexing, automation, and high-throughput screening.

MicroRNAs MicroRNAs (miRNAs) constitute a novel class of small, noncoding endogenous RNAs that regulate
(miRNAs) gene expression by directing their target mRNAs for degradation or translational repression.
miRNAs, which are found in plants, animals, and some viruses, are usually just 22 nucleotides long.
miRNAs were initially identified in Caenorhabditis elegans in 1993. Seven years later, another class
of short RNAs [small interfering RNAs (siRNAs)] was discovered. (miRNAs are formed from regions of
RNA transcripts that fold back on themselves to form short hairpins; siRNAs are formed from longer
regions of double-stranded RNA.) When it became clear that siRNAs participate in RNA interference,
the regulatory richness of small RNAs began to be appreciated. It is now recognized that miRNAs
play roles in cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative
diseases. They are also finding use as biomarkers.

Molecular Molecular diagnostics are used to assess disease prognosis and therapy response. They detect
Diagnostics specific sequences in DNA or RNA that may or may not be associated with disease, including single-
nucleotide polymorphisms, deletions, rearrangements, insertions, and others. Most MDx are
focused on oncology, virology, microbiology, and blood screening.
Monoclonal Monoclonal antibodies (mAbs) are antibodies produced by a hybrid cell line, a kind of clone called a
Antibody hybridoma. Each hybridoma culture consists of genetically identical cells that produce identical
(mAb) antibodies. In contrast, polyclonal antibodies are made from several different immune cells that
produce different antibodies. mAbs serve as experimental probes in cell biology, biochemistry, and
parasitology, and are used in purification of biological substances and certain drugs. They can be
made in large quantities and are used to treat many diseases, including some types of cancer.

Next- Next-generation sequencing (NGS), also referred to as massive parallel sequencing, is a high-
Generation throughput sequencing technique that differs from traditional Sanger sequencing in that it can
Sequencing sequence millions of DNA strands in parallel. This method yields substantially more results in a
(NGS) shorter time and minimizes the need for the fragment-cloning method often used by traditional
sequencing platforms. While the engineering and chemistry differ per instrument, fundamentally,
most platforms will sequence massive numbers (up to 43 billion in some cases) of short DNA strands
(50–400 bp) per instrument run.

Nuclear Nuclear magnetic resonance (NMR) spectroscopy is an analytical technique that uses the magnetic
Magnetic properties of various atomic nuclei—related in part to the presence of nuclear spin states that
Resonance possess different energies in an external field magnetic field—to determine the physical and
(NMR) chemical properties of the organic or inorganic compound being analyzed.
Spectroscopy

Oligonucleo- Oligonucleotides are short, single-stranded nucleic acid polymers, usually made up of 13 to 25
tides nucleotides, and are designed to hybridize specifically to DNA or RNA sequences. These small bits of
nucleic acids can be manufactured as single-stranded molecules with any user-specified sequence
and are widely used in PCR, DNA sequencing, library construction, and as molecular probes.
Oligonucleotides are used as probes for detecting specific sequences that are complementary to the
oligonucleotides. When a certain sequence needs to be detected, a complementary oligonucleotide
is synthesized. It is then bound to a fluorescent marker and allowed to bind to the specific segment
of RNA or DNA it was designed to detect.

Optogenetics Optogenetics is a biological technique in which various cellular genes have been engineered to be
controlled selectively to switch on or off in the presence of a specific wavelength of light.

Orphan Drugs An orphan drug is a therapeutic that has been developed to treat a rare medical disorder known as
an orphan disease. Because there is usually no major profit incentive involved in the development of
orphan drugs, regulatory authorities encourage their discovery and development by offering
accelerated marketing approval for an orphan drug and a longer period of product exclusivity.

Pathway Pathway analysis refers to bioinformatics approaches and software used to identify related proteins
Analysis within a biochemical pathway—often employed when studying differential gene expression for
disease.

Peptides Peptides are short chains of amino acid monomers linked by peptide (amide) bonds, in which a
nitrogen atom of one amino acid binds to the carboxyl carbon atom of another. Peptides are often
classified according to the number of amino acid residues. Oligopeptides have 10 or fewer amino
acids. Molecules consisting from 10 to 50 amino acids are called peptides. Peptides have a wide
range of applications in medicine and biotechnology. They regulate most physiological processes,
acting at some sites as endocrine or paracrine signals and at others as neurotransmitters or growth
factors.
Pharmaco- Once it was learned genetic makeup can have a major impact on how a person will respond to a
genomics drug, the field of pharmacogenomics was established. Pharmacogeomics studies the relationship
between an individual’s genetic profile and that individual’s corresponding drug metabolism and
response. Ultimately, it is hoped that pharmacogenomics will allow a doctor to prescribe the most
appropriate drug at a dose that will maximize the benefits while minimizing the risk.

Pharmaco- Pharmacokinetics (PK) is the time study of the absorption, distribution, metabolism, and excretion
kinetics/ (ADME) of a drug. Pharmacodynamics (PD) is the study of the effects of a drug and its specific
Pharmaco- mechanism of action. Dose–response relationships are of particular interest. The two techniques are
dynamics often combined to determine the optimum dose of a drug for a patient.
(PK/PD)

Phenotypic Phenotypic screening is a drug discovery technique used in animal models and cell-based assays for
Screening identifying biological or small molecules with properties that alter a phenotype in a particular
manner. The phenotypic screening closely mimics the in vivo state, thus many researchers believe
the methodology presents the best opportunity to improve the drug discovery process significantly.

Point-of-Care Point-of-care testing allows patient diagnoses in the physician’s office, an ambulance, the home, the
Testing field, or in the hospital by means of portable or handheld instruments and analyzers. This differs
from traditional testing, which typically involves the transport of samples to medical laboratories,
and the use of testing procedures that can take hours or days. The results from point-of-care tests,
on the other hand, are timely and allow rapid treatment to the patient.

Polymerase Polymerase chain reaction (PCR) is a molecular biology technique that is used to amplify small
Chain Reaction amounts of DNA exponentially, generating thousands to millions of copies of the input DNA
(PCR) sequence. The method relies on thermal cycling that repeatedly heats and cools the reaction to
separate, or melt, the complementary DNA strands, anneal short DNA primers that are
complementary to the separated DNA template, and enzymatically replicate the DNA starting from
the annealed primers. The key to this reaction is the use of a thermostable DNA polymerase
molecule that can withstand the repeated high melting temperatures (~95°C) and has reasonably
high fidelity.

Prenatal/ Prenatal testing provides information about a baby's health before birth. Some routine tests during
Postnatal pregnancy also check on the mother’s health. Screening tests such as ultrasound, chorionic villus
Testing sampling, cell-free fetal DNA testing, amniocentesis, glucose screening, and cystic fibrosis carrier
screening detect risks for or signs of possible health problems in the mother or her baby. Postnatal
testing is used to detect chromosomal and genomic abnormalities and can be performed on
peripheral blood, cord blood, products of conception, and saliva.

Post- Post-translational modification (PTM) is the process whereby proteins are modified enzymatically
Translational during or after they are synthesized in a cell. PTM mechanisms include phosphorylation,
Modification glycosylation (eukaryotic proteins), and lipidation. PTMs are known to play important roles in cell
signaling. A number of techniques are used to detect the PTM of proteins, including mass
spectrometry, Eastern blotting, and Western blotting.
Protein Proteins exist with specific structural, biochemical, electromagnetic, spectroscopic, and
Character- thermodynamic properties; therefore, they can be characterized accordingly with the use of a
ization variety of methods, such as mass spectrometry, sedimentation, light scattering, circular dichroism,
and isothermal titration calorimetry. The goal is to learn as much as possible about a protein’s
structural and functional attributes during a new drug discovery and development process for
potential therapeutic applications.

Protein Protein purification involves a variety of steps to isolate one or several proteins from a mixture of
Purification usually cells, tissues, or entire organisms. The purification process allows the characterization of the
structure, function, and interactions of a protein of interest. Protein purification can be carried out
on the basis of protein solubility, size, charge, and binding affinity. Common techniques for purifying
proteins are dialysis and chromatographic approaches such as gel-filtration, ion-exchange, and
affinity chromatography.

Proteins Proteins are large biomolecules that play many critical roles in the body, including catalyzing
metabolic reactions, DNA replication, and transporting molecules. They do most of the work in cells
and are required for the structure, function, and regulation of the body’s tissues and organs.
Proteins are made up of hundreds or thousands of amino acids. There are 20 different amino acids
that can be combined to make a protein, and this linear protein structure folds into a unique 3D
structure that determines each protein’s activity.

Proteomics Proteomics is the large-scale study of a specific proteome—the entire set of proteins expressed by
an organism or cellular system—including information on protein abundances, their variations and
modifications, along with their interacting partners and networks. Proteomics has been enabled by
the accumulation of both DNA and protein sequence databases, improvements in mass
spectrometry, and the development of computer algorithms for database searching. Proteomic
techniques can be applied to clinical specimens to study diseases such as cancer.

Reagents Reagents are chemical compounds or substances that are used to detect and identify another
substance, by means of a chemical reaction, during a specific testing procedure. Reagents are
utilized across the entire range of biotechnology R&D and in commercial applications. The growth of
the instrumentation market continues to largely determine the demand for reagents.

RNA RNA (ribonucleic acid) is a molecule similar to DNA, but unlike DNA it comes in a variety of shapes
and types and is usually single-stranded. An RNA strand has a backbone made of alternating sugar
(ribose) and phosphate groups. Attached to each sugar is one of four bases—adenine (A), uracil (U),
cytosine (C), or guanine (G). There are many types of RNAs that are involved in protein synthesis
(e.g., messenger, transfer, and ribosomal RNAs), post-transcriptional modification and DNA
replication (e.g., snRNA, sno RNA, gRNA), and gene regulation (e.g., lncRNA, siRNA) as well as
parasitic RNAs (e.g., retrotransposons, satellite RNA, RNA viral genomes).

RNA RNA interference (RNAi) is a normal biological process that cells use to regulate and/or inhibit gene
Interference expression through the degradation of mRNA molecules. RNAi pathways exist in most eukaryotes
(RNAi) and consist of several conserved proteins (including Dicer and Argonaute) that are integral to the
interference pathway. In recent years scientists have exploited this technique as a molecular biology
tool and as the basis for developing therapeutic drug compounds.
RNA RNA sequencing (RNA-seq) is a next-generation sequencing technique, also called whole-
Sequencing transcriptome shotgun sequencing, that is used to analyze and quantify the transcriptome, as well as
(RNA-Seq) identify alternative gene spliced transcripts, post-transcriptional modifications, gene fusions,
mutations/SNPs, miRNAs, tRNAs, and ribosomal profiling studies.

Sequencing Sequencing, in the life sciences, has come to mean the determination of the atomic-level structure
of the molecule in question. Sequencing can be applied to various types of biomolecules, such as
DNA, RNA, proteins, or polysaccharides. In practice, the term has taken on the meaning of
elucidating the proper order of the constituents that make up the biomolecule (nucleotides, amino
acids, etc.).

Single-Cell Single-cell genomics is the sequencing and analysis of an individual cell’s genome, transcriptome,
Genomics proteome, metabolome, etc. Advances in next-generation sequencing have allowed for this
technique to rise in prominence, providing a glimpse into the heterogeneity that exists between
normal and diseased cell populations.

Single-Use Single-use systems, sometimes referred to as disposables, are used in biomanufacturing applications
Systems to reduce time and costs associated with the manufacture of therapeutic proteins. Single-use
bioreactors contain the product-producing cell line and cell culture media, whereas single-use bags
are relied upon for sterile filling and therapeutic product transport. Single-use instruments are
increasingly replacing traditional steel biomanufacturing systems.

Synthetic Synthetic biology draws on multiple academic disciplines to stage a coordinated advance toward two
Biology goals: (1) the design and construction of the core components of new biological entities such as
enzymes, genetic circuits, and cells; and (2) the redesign of existing biological systems. Advances in
chemistry, biology, computer science, and engineering have enabled synthetic biology tools to
change how we build biological systems. Recent developments have allowed scientists to make new
sequences of DNA from scratch and re-engineer cells to enhance production of biologic drugs and
create novel biosensors for diagnostics and drug testing.

Systems Systems biology is the computational and mathematical modeling of complex biological systems. It
Biology focuses on interactions within those systems. Historically, most systems biology efforts have looked
at generating models at the cellular level to provide a better understanding of intracellular
processes. For example, models of genetic regulatory networks helped shed light on how
intracellular genes and proteins interact with each other to govern cellular behaviors and decisions.

Target-Based Target-based screening is a drug discovery technique that focuses on specific proteins that have
Screening been associated with particular diseases. Target-based screening uses biochemical or cell-based in
vitro assays in combination with high-throughput screening methods and compound libraries.
Criticism of the technique for not improving the productivity of new drug discovery efforts has led to
the wider adoption of a competitive technology known as phenotypic screening.

Transcription Transcription activator-like effector nucleases (TALENs) are engineered restriction enzymes that fuse
Activator-Like transcription activator-like (TAL) effector DNA-binding domains to a DNA cleavage domain. These
Effector nucleases can be designed to bind and cut practically any DNA sequence. Along with zinc finger
Nucleases nucleases and CRISPR/Cas9, TALENs are an integral part of the genome editing molecular toolkit.
(TALENs)
Transcriptome The transcriptome is the ensemble of all the RNA transcripts (mRNA) within a single cell or a
population of cells. The transcriptome actively reflects all genes being expressed at a given time
point and can vary with external environmental conditions, unlike the genome which is relatively
fixed within cells.

Transfection Transfection is the process of delivering nucleic acids (DNA or RNA) into eukaryotic cells by nonviral
means. Delivery methods typically include either electroporation (creating transient pores in the cell
membrane using electrical current) or the use of chemical reagents such as cationic lipids that fuse
with the cell membrane, carrying the genetic cargo inside.

Transgenics Transgenics notes an organism that contains a gene or genetic material that has been naturally
transferred or artificially engineered from a different organism. This technique can be applied to
most any organism (bacteria, plants, animals, etc.) and has the potential to change the phenotype of
the organism to which the new genetic material was introduced. The term is used interchangeably
with genetically modified organisms (GMOs).

Western Blot Western blot is an analytical technique (sometimes called the protein immunoblotting) that uses gel
electrophoresis to separate proteins based on their 3D structure (native proteins) or by their
molecular weight (denatured proteins). The separated proteins are then transferred to a membrane
where the specific proteins of interest are detected using antibodies conjugated to chemicals that
allow for visualization.

Zinc Finger Zinc finger nucleases (ZFNs) are engineered restriction enzymes that fuse a zinc finger—a protein
Nucleases motif stabilized by zinc ions—DNA-binding domain to a DNA-cleavage domain. These nucleases can
(ZFNs) be designed to target specific DNA sequences. Along with the CRISPR and TALEN techniques, ZFNs
are essential tools in the genome editing molecular toolkit.

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