Apoptosis

(AM500000)

Number of cells undergoing programmed cell death in a particular tissue

Immunohistochemistry; TUNEL assay; Fluorescence microscopy; Acridine orange staining; Western blot; Cell survival analysis; Detection of apoptosis using the TUNEL assay; Wound healing assay; Expression of cleaved caspase-3 (cC3); Histology; Induced liver injury by carbon tetrachloride

Amino acid levels

(AM900000)

Levels of amino acids, organic compounds with amine and carboxylic acid functional groups, which are building blocks for proteins and some can also act as neurotransmitters

Ion-exchange chromatography; High-performance liquid chromatography (HPLC)

Calcium ion uptake

(AM900005)

Influx of calcium ions in cells, from extracellular space or intracellular calcium stores, typically through channels or transporters

Measurement of sarcoplasmic reticulum calcium uptake; Calcium imaging; Fluorescence microscopy

Cell adhesion

(AM900006)

Ability of a cell to adhere to another cell or to a non-cellular component of the environment

RNA sequencing; Gene expression microarray; Immunohistochemistry; Immunocytochemistry; Confocal microscopy

Cell differentiation

(AM900007)

Process of fate determination of progenitor (totipotent) cells to partial or fully differentiated cell types

Immunohistochemistry; Quantitative PCR (qRT-PCR)

Cell proliferation

(AM900008)

Rate of growth or division of undifferentiated cells, including stem cells and other progenitor cells

Immunohistochemistry; EdU incorporation; phospho-Histone 3 expression; Fluorescence microscopy; Cell counting; Alcian blue/alizarin red staining; General observations; Histology; Immunostaining; Flow cytometric analysis; Feulgen staining; Gene expression microarray

Chemotaxis

(AM900009)

Directed movement of a mobile cell guided by a specific chemical concentration gradient

In vitro splenic T cells chemotaxis

Chromatin modification

(AM900010)

Changes in any of the components of chromatin, such as the histones in nucleosomes, which may alter the ultrastructure of the chromatin to make DNA more or less accessible for biological processes like replication and transcription

Chromatin immunoprecipitation (ChIP); RNA sequencing; Formaldehyde-assisted isolation of regulatory elements (FAIRE)/quantitative PCR (qPCR); Chromatin immunoprecipitation sequencing (ChIP-seq); Western blot; Quantitative PCR (qRT-PCR); Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq); DNase I hypersensitive sites sequencing (DNase-seq)

Cytoskeletal organization

(AM900011)

Organization of any of the components of the cytoskeleton, including microfilaments (actin), intermediate filaments and microtubules

Immunostaining; Western blot; Microscopic analysis; Confocal microscopy; Gene expression microarray

DNA methylation

(AM900012)

Covalent transfer of a methyl group to either N-6 of adenine or C-5 or N-4 of cytosine of DNA

Methylation-sensitive restriction enzyme assay; Dot-blot analysis; Nearest neighbor analysis; Autoradiographic analysis; CpG methylomics analysis

DNA repair

(AM900013)

Process of restoring DNA after damage or replication error

Immunohistochemistry; Immunostaining; X-ray irradiation induced DNA repair; Gene expression microarray

Cell senescence

(AM900014)

Process in which a cell progresses from its inception to the end of its lifespan, which occurs as the cell continues cycles of growth and division

Immunohistochemistry; Lipofuscin accumulation

Enzyme activity

(AM900015)

Ability of any enzyme to perform catalysis, especially in enzymes extracted from animals to test in an in vitro assay immediately

Measurement of enzyme activity; Western blot; Mitochondrial respiratory chain enzyme analysis; Enzyme assay; Cell counting; Immunoprecipitation; Spectrophotometry; Immunohistochemistry; Hexosaminidase assay; Fluorescence microscopy; High-performance liquid chromatography (HPLC)

Gene expression

(AM900016)

Expression levels of genes, determined by RNA quantification

Immunohistochemistry; Quantitative PCR (qRT-PCR); Gene expression microarray; Northern blot; Complementary DNA (cDNA) macroarray; In situ hybridization (ISH); RNase protection assay; Whole-mount immunohistochemistry; Semi-quantitative PCR (qRT-PCR); RNA sequencing; Nuclear run-on assay; Western blot; Immunostaining; Chromatin immunoprecipitation (ChIP); Polysome profiling; Flow cytometric analysis; Polymerase chain reaction (PCR); Differential display analysis of hippocampus

Loss of heterozygosity (LoH)

(AM900019)

Loss of a single functional allelle, on a locus with only one copy of a particular gene, leading to the deletion of this chromosomal locus in a specific population of somatic cells

Southern blot

Marker expression

(AM900020)

Expression of protein markers in tissue or cell samples to ascertain normal organization, patterning or differentiation state of extracted tissue or cells

Quantitative PCR (qRT-PCR); Western blot; Immunostaining; Immunohistochemistry; In situ hybridization (ISH); TUNEL assay; Mass spectrometry (MS)

Metabolite level quantification

(AM900022)

Levels of metabolic byproducts

In vitro diagnostic tests; Gas chromatography-mass spectrometry (GC-MS); High-performance liquid chromatography (HPLC); Nitrate level assay; Glutathione level assay

Metabolite levels: neurometabolites

(AM900023)

Levels of metabolic byproducts in the nervous system

Proton NMR; High-performance liquid chromatography (HPLC)

Micro-RNA biogenesis

(AM900024)

Process of maturation of micro-RNA, starting with transcription, going through Drosha and Dicer cleavages, and formation of the RNA-induced silencing complex (RISC)

Gene expression microarray

Mitochondrial biogenesis

(AM900025)

Growth and division of preexisting mitochondria in a cell

Flow cytometric analysis; Mitochondrial respiratory chain enzyme analysis

Mitochondrial DNA replication

(AM900026)

Process whereby new strands of mitochondrial DNA are synthesized

Quantitative PCR (qRT-PCR)

Protein binding

(AM900028)

Binding of two or more proteins that are required to associate or form an enzyme or bioactive complex to perform a function. This includes formation active transcriptor factor complexes, and binding of ligand to receptors for activation of receptors or signaling. It does not include any receptor binding studies used to estimate expression levels of receptor in any tissue.

Immunoprecipitation; Agonist-stimulated G-protein coupling assay; Co-immunoprecipitation; In situ ligand binding studies; Cranial computerized tomography (CT) scan; Autoradiographic analysis; Radioligand binding studies; Western blot

Protein binding: Bmax of receptor

(AM900029)

Greatest attainable concentration of bound ligand and receptor, Bmax=[R]+[L*R], where [R] is concentration of free receptor, and [L*R] is concentration of bound ligand and receptor

Receptor saturation binding assay; Radioligand binding studies

Protein binding: Kd of receptor

(AM900030)

KD is the ligand-receptor affinity and measures the strength of biomolecular interactions, it may also be measured for antibody antigen interactions. It is also called the equilibrium dissociation constant, KD=koff/kon=([L]*[R])/[L*R], where [L] is concentration of free ligand, [R] is concentration of free receptor, and [L*R] is concentration of bound ligand and receptor

Receptor saturation binding assay; Radioligand binding studies

Protein expression level evidence

(AM900031)

Expression level of proteins, determined by protein quantification using any type of densitometry or indirect methods like co-immunoprecipitation

Immunoprecipitation; Western blot; Immunohistochemistry; Peak-scaled non-stationary fluctuation analysis; Fluorescence microscopy; Immunocytochemistry; Liquid chromatography-mass spectrometry (LC-MS); Immunostaining; Histology; Radioligand binding studies; In situ hybridization (ISH); Quantitative PCR (qRT-PCR); Long term potentiation (LTP); Laser scanning cytometry; ELISA; Gas chromatography-mass spectrometry (GC-MS); Chromatin immunoprecipitation sequencing (ChIP-seq); Enzymatic measurement of lactate in retinas; High-performance liquid chromatography with electrochemical detection (HPLC-EC); Metabolic labeling of proteins; High-performance liquid chromatography (HPLC); Semi-quantitative PCR (qRT-PCR); Autoradiographic analysis; Zymography; Northern blot; Fractionation; Polymerase chain reaction (PCR)

Protein expression: in situ protein expression

(AM900032)

Expression of a specific protein, by labeling in the tissue or cell of origin and visualized by microscopy

Western blot; Immunocytochemistry; Immunohistochemistry; Immunostaining; Immunofluorescence staining; Autoradiographic analysis; In situ hybridization (ISH); Quantitative PCR (qRT-PCR); Lectin histofluorescence

Protein localization: nucleus

(AM900033)

Targeting of cellular proteins to the nucleus or nuclear membrane

Immunohistochemistry; Fractionation; Fluorescence microscopy

Protein localization: synapse

(AM900034)

Targeting and maintenance of synaptic proteins, such as receptors, scaffolding proteins and transporters

Western blot; Immunohistochemistry; Fractionation; Immunostaining; Fluorescence microscopy; Quantitative PCR (qRT-PCR); Histology; Radioligand binding studies

Protein modification process

(AM900035)

Assessment of levels of post-translational protein modifications, including folding into native state, reversible chemical alterations like disulfide bonds, phosphorylation, acetylation, hydroxylation, methylation and carboxylation and irreversible chemical alterations like cleavage and protein splicing

Immunohistochemistry; Western blot; Morris water maze test; In situ hybridization (ISH); Mitochondrial oxygen consumption studies; Liquid chromatography-mass spectrometry (LC-MS)

Protein phosphorylation

(AM900036)

Posttranslational modification of proteins consisting in the covalent bonding of phosphoryl groups, including activating/inactivating phosphorylation carried out by kinases on Ser/Thr/Tyr residues on enzymes

Western blot; ELISA; Fractionation; Immunohistochemistry; Reciprocal social interaction test; Long term potentiation (LTP); Densitometric analysis

Protein ubiquitination

(AM900037)

Posttranslational modification of proteins consisting in the covalent bonding of ubiquitin

Immunoprecipitation; Western blot; Gene expression microarray

Protein-DNA complex assembly

(AM900038)

Binding of proteins to specific sequences of DNA, like promoter or enhancer regions leading to changes in gene expression, or histone structure

Chromatin immunoprecipitation sequencing (ChIP-seq); Immunofluorescence staining; Chromatin immunoprecipitation (ChIP); Western blot; Quantitative PCR (qRT-PCR)

Proteomic profile diversity

(AM900039)

Dynamic composition of proteins found in different cell types, identified from whole cells in tissues or specific cellular compartments using high throughput techniques

Liquid chromatography-mass spectrometry (LC-MS); Two-dimensional gel electrophoresis (2-DGE)

Regulation of gene expression

(AM900040)

Regulation of transcription initiation, continuation and termination, including non-sense mediated decay

Western blot; Quantitative PCR (qRT-PCR); ELISA; Immunohistochemistry; RNA sequencing; Immunoprecipitation; Long term potentiation (LTP); Gene expression microarray; Northern blot; RNase protection assay; Immunocytochemistry

Regulation of translation

(AM900041)

Regulation of translation initiation, continuation and termination, formation of the ribosome complex, capping of mRNA for translation

Autoradiographic analysis; Gene expression microarray; Polysome profiling; Quantitative PCR (qRT-PCR); Western blot; Fluorescent non-canonical amino acid tagging (FUNCAT); Metabolic labeling of proteins; Immunohistochemistry; Surface sensing of translation (SUnSET); Semi-quantitative PCR (qRT-PCR); RNA sequencing

RNA modification

(AM900042)

Posttranscriptional changes in RNA

Signaling

(AM900043)

Cellular system of communication in response to extracellular or environmental cues, acting through second messengers and post-translational modifications that lead to changes in cellular function, such as altered gene expression

Western blot; ELISA; Immunoprecipitation; Fluorescence tomography; Immunohistochemistry; Quantitative PCR (qRT-PCR); Gene expression microarray; Two-dimensional flourescence difference gel electrophoresis (2-DIGE)

Targeted expression

(AM900044)

Expression level of the protein (and /or its transcript) targeted by genetic manipulation in the model

Western blot; Immunohistochemistry; In situ hybridization (ISH); Semi-quantitative PCR (qRT-PCR); Histology; Quantitative PCR (qRT-PCR); Immunostaining; RNA sequencing; Immunoprecipitation; Polymerase chain reaction (PCR); Immunofluorescence staining; Northern blot; DNA sequencing; T7 endonuclease assay; Enzyme assay; Southern blot; Neuronal and non-neuronal cell fractionation; Fluorescence microscopy; Radioligand binding studies; Flow cytometric analysis; Immunocytochemistry; Radioimmunoassay (RIA); Histological analysis; Confocal microscopy

Transcriptome diversity

(AM900045)

Analysis and comparison of entire transcriptomes of cells or tissues

Western blot; Gene expression microarray; Quantitative PCR (qRT-PCR)

Micronutrient level: mineral: zinc

(AM900046)

Analysis of trace levels of mineral zinc in the circulation or in tissues

Immunohistochemistry

Protein aggregation: neuronal

(AM900049)

Aggregation or deposition of misfolded proteins into complex polymers or fibrils inside or around neurons

Western blot; Fractionation; Immunohistochemistry

Signaling: Wnt pathway

(AM900054)

Increased expression or activation of the protein components that are involved in Wnt/Frizzled-initiated cellular signaling pathways

RNA sequencing; Quantitative PCR (qRT-PCR); Luciferase reporter assay; Western blot; Gene expression microarray

Micronutrient level: mineral

(AM900055)

Analysis of trace levels of mineral nutrients in the circulation or in tissues, like Cu, Se, Mg, Mn etc (exception Zn and other mineral strongly associated with ASD)

Mass spectrometry (MS)

Protein localization: cytosol

(AM900056)

Targeting of cellular proteins to the cytosol, cytosolic organelle or cell membrane

Fractionation; Western blot; Immunohistochemistry; Fluorescence microscopy

Signaling: PI3K/AKT pathway

(AM900057)

Expression or activation of the protein components that are involved in PI3K/AKT signaling pathways

Western blot

Cell differentiation: hematopoiesis

(AM900058)

The cell differentiation process leading to the generation of all blood cells

Histology; Flow cytometric analysis; Hematological analysis

Gene expression: alternative splicing

(AM900059)

transcript expression levels of alternatively spliced alleles quantified by number of alternative splicing events with percent spliced in (PSI), percent intron retention (PIR), or percent splice site usage (PSU) changes

RNA sequencing; Quantitative PCR (qRT-PCR)

Chromatin modification: histone modification: open chromatin

(AM900060)

Modifications of histone proteins that leads to increased accessibility of DNA and regulatory elements, increased open chromatin is associated with transcription promotion

DNase I hypersensitive sites sequencing (DNase-seq); Chromatin immunoprecipitation sequencing (ChIP-seq)

Signaling: mTOR pathway

(AM900061)

Mammalian target of rapamycin (mTOR) signaling pathway, known to be involved in growth, proliferation, angiogenesis, T-cell activation, adipogenesis. mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC 2) are two known multi-protein complexes that regulate different processes involving mTOR signaling. mTORC1 is known to postiively regulate autophagy, protein and lipid synthesis etc., mTORC2 is involved in cytoskeletal organization,while both mTORC1 and mTORC2 are involved in cell proliferation.

Western blot

Signaling: amino acid response pathway

(AM900062)

Amino acid response (AAR) is the pathway triggered in mammalian cells by amino acid starvation, which includes a t-RNA acivated sensor kinase (GCN2), eIF2alpha phosphorylation on serine-51, and selected translations of ATF4, ATF5, and GADD34

RNA sequencing

Macroautophagy

(AM900063)

Process of degradation of intracellular organelles using the lysosomal pathway or vacuoles

Immunostaining

Protein localization: membrane

(AM900065)

Targeting of cellular proteins to the cell membrane

Fractionation; Western blot; Immunohistochemistry

Signaling: MAPK pathway

(AM900066)

Activation of the MAPK signaling pathway, which can be measured by ERK1 or ERK2 phosphorylation but also by phosphorylation of upstream and downstream factors, small GTPase activity, secondary messenger signaling and target gene expression

Protein localization: endoplasmic reticulum

(AM900067)

Targeting, localization or retention of a protein in or on the endoplasmic reticulum.

Signaling: UPR pathway

(AM900068)

Activation of the conserved unfolded protein response pathway, a cellular response to ER stress.

Protein degradation: proteasome

(AM900069)

Degradation ofubiquitinated proteins by the proteasome.

Chromatin modification: histone acetylation

(AM900070)

The modification of a histone by the addition of an acetyl group.

Signaling: PKC pathway

(AM900071)

Any process that modulates the frequency, rate or extent of protein kinase C activity.

Signaling: PKA pathway

(AM900072)

Expression or activation of the components involved in cAMP-dependent PKA cellular signaling cascade which includes a series of reactions mediated by the intracellular serine/threonine kinase protein kinase A.

Signaling: Notch pathway

(AM900073)

Expression or activation of the genes or proteins that constitute the Notch signaling pathway

Western blot, RNA sequencing

Gene expression: wnt pathway

(AM900074)

transcript expression levels of genetic components of the wnt signaling pathway

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: neurite outgrowth

(AM900075)

transcript expression levels of genes regulating neurite growths

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: herpes simplex virus infection

(AM900078)

transcript expression levels of genes activated in response to herpes simplex infection

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: autoimmune thyroid disease pathways

(AM900079)

transcript expression levels of components of the autoimmune thyroid disease pathways

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: neurodegeneration

(AM900080)

transcript expression levels of genes implicated in neurodegenration

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: activated microglia

(AM900081)

transcript expression levels of polarized or activated states of microglia

RNA sequencing; Quantitative PCR (qRT-PCR)

Gene expression: leukocyte mobility

(AM900082)

transcript expression levels of gene regulating leucocyte mobility and migration

RNA sequencing; Quantitative PCR (qRT-PCR)

Differential gene expression

(AM900083)

abnormal expression of clusters or families of genes defined by reported a GEO or SRA accession number

RNA sequencing; Quantitative PCR (qRT-PCR)

Signaling: hedgehog pathway

(AM900084)

A series of molecular signals generated as a consequence of activation of the transmembrane protein Smoothened, responsible for transmiting information for proper cell differentiation.

Mitochondrial activity

(AM900085)

Function of cellular organelles responsible for energy production

Mitochondrial respiratory chain enzyme analysis; Superoxide generation assay

Mitochondrial function

(AM900088)

Function of cellular organelles responsible for energy production

Mitochondrial respiratory chain enzyme analysis; Spectrophotometry

Mitochondrial proton-transporting ATP synthase complex assembly

(AM900092)

Organization and bonding together of a proton-transporting ATP synthase subunits in the mitochondrial inner membrane.

Native non-denaturing polyacrylamide gel electrophoresis

Mitochondrial proton-transporting ATP synthase complex, catalytic sector F(1)

(AM900093)

The catalytic sector of the mitochondrial hydrogen-transporting ATP synthase that comprises the catalytic core and central stalk and is peripherally associated with the mitochondrial inner membrane when the entire ATP synthase is assembled.

Western blot; Immunostaining; Quantitative PCR (qRT-PCR); Immunohistochemistry

Mitochondrial proton-transporting ATP synthase complex, coupling factor F(o)

(AM900094)

All non-F1 subunits of the mitochondrial hydrogen-transporting ATP synthase, including integral and peripheral mitochondrial inner membrane proteins.

Western blot; Immunostaining; Quantitative PCR (qRT-PCR); Immunohistochemistry

Mitochondrial reactive oxygen species

(AM900095)

MItochondrial levels of unstable molecules or free radicals that contains oxygen and easily reacts with other molecules in a cell, potentially causing damage to DNA, RNA, and proteins, and cell death. Increase in reactive oxygen species may occur due to an increase in mitochondrial enzyme activity or due to a decrease in ROS removal mechanisms.

Superoxide generation assay

Tricarboxylic acid cycle

(AM900096)

universal metabolic pathway of aerobic respiration in which the acetyl group of acetyl coenzyme A is oxidized to two CO2 and four pairs of electrons are transferred to coenzymes; the acetyl group combines with oxaloacetate to form citrate, which undergoes successive transformations to isocitrate, 2-oxoglutarate, succinyl-CoA, succinate, fumarate, malate, and oxaloacetate again, thus completing the cycle

Liquid chromatography-mass spectrometry (LC-MS)

Glycolysis

(AM900097)

Catabolic process that begins with the conversion of glucose to glucose-6-phosphate by glucokinase activity resulting in the breakdown of a carbohydrate into pyruvate and a small amount of ATP.

Protein localization: dendritic spines

(AM900098)

Targeting of neuronal proteins to the dendritic spines

Immunohistochemistry

Transcriptionally active chromatin

(AM900099)

The ordered and organized complex of DNA and protein that forms regions of the chromosome that are being actively transcribed.

Signaling: calcium

(AM900102)

Change in expression or activation of proteins in calcium-mediated signal transduction

Differential gene expression: ASD risk genes

(AM900103)

Abnormal expression of clusters or families of genes linked to increased risk for autism spectrum disorder, such as SFARI, AutismKB

DNA modification

(AM900104)

The covalent alteration of one or more nucleotide sites in DNA, resulting in a change in its properties

Dot blot

Differential protein expression

(AM900105)

Abnormal expression of proteins studied in a high-throughput experiment

Tandem mass tag (TMT)-labeled quantitative proteomics

Phagocytosis

(AM900106)

A vesicle-mediated transport process that results in the engulfment of external particulate material by phagocytic cells, such as microglia, and their delivery to the lysosome

Signaling: nitric oxide pathway

(AM900107)

Change in expression or activation of proteins in nitric oxide-mediated signal transduction

Transcriptionally active chromatin

(AM900108)

The ordered and organized complex of DNA and protein that forms regions of the chromosome that are being actively transcribed.

Post-synaptic density number

(AM900109)

Number or density of the protein dense specialized structure attached to the post-synaptic membrane at the synapse

Neuronal activity dependent gene regulation

(AM1200105)

Activity-dependent signalling pathways induce neuronal gene transcription by modulating the function of both transcriptional activators and repressor

Western blot; Long term depression (LTD); Quantitative PCR (qRT-PCR); Luciferase reporter assay

Neuronal activity dependent transcription

(AM1200138)

Neuronal activity-dependent signalling pathways induce neuronal gene transcription by modulating the function of both transcriptional activators and repressor

Neuronal activity dependent phosphorylation

(AM1200150)

changes in protein phosphorylation upon synaptic stimulation e.g. synaptic stimulation mediated by D-serine

Western blot

Neuronal activity dependent translation

(AM1200151)

changes in protein translation upon synaptic stimulation e.g. synaptic stimulation mediated by D-serine

Western blot