Table 2 Terms used in NeuroGeM

Organism

D. melanogaster

Three model organisms

C. elegans

S. cerevisiae

Gene ID

FBgn------

Primary IDs used in the respective genome databases (FlyBase, WormBase, and SGD). These IDs are also used as primary IDs in NeuroGeM.

W--------

S---------

Type of modification

Suppressor

Suppressors are those genes that alleviate disease pathology or slow disease progression when over-expressed, and those that aggravate disease pathology or accelerate disease progression when down-regulated or deleted. Enhancers are those genes that alleviate disease pathology when down-regulated, and those that aggravate pathology when over-expressed. Non-modifiers have no effect on disease progression.

Enhancer

Non-modifier

Mode of action

Toxicity modification

Toxicity modifiers are those genes that change disease pathology. Aggregation modifiers are those genes that change the size or number of protein aggregates.

Aggregation modification

Disease model

Alzheimer’s disease (AD)

ND models compiled in the current version of NeuroGeM. We divided AD into the subtypes AD_Tau and AD_Aβ according to the gene used to induce the disease phenotype (mutant Tau protein and Aβ42, respectively).

Huntington’s disease (HD)

Parkinson’s disease (PD)

Spinocerebellar ataxia type 1 (SCA1)

Spinocerebellar ataxia type 3 (SCA3)

Spinocerebellar ataxia type 7 (SCA7)

Amyotrophic lateral sclerosis (ALS)

PolyQ disease (PolyQ)

Disease induction

Various

This field contains expression cassette information described in the literature including promoter and disease-causing gene (e.g. polyQ stretch length).

Disease-causing mutant proteins compiled in NeuroGeM are Aβ and tau protein for AD, SOD1 for ALS, huntingtin for HD, α-synuclein for PD, Ataxin-1 for SCA1, Ataxin-3 (MJD) for SCA3, Ataxin-7 for SCA7 and polyQ stretches for the PolyQ disease model.

Modulation method

Overexpression

This field describes whether the expression level of the target gene increased (overexpression or gain-of-function) or decreased (knockdown, knockout, or loss-of-function). We adopted the same terms used in the original articles.

Gain-of-function

Knockdown

Knockout

Loss-of-function

Experimental scale

Primary high-throughput

This field describes the scale of the experiments. Experiments that were not high-throughput (HT) were assigned as low-throughput (LT). Experiments performed in primary screens were assigned as Primary high-throughput. Experiments to confirm the results obtained from the Primary high-throughput screens were assigned as Secondary high-throughput.

Secondary high-throughput

Low-throughput

Measurement

Various

This field describes how the change of pathology was evaluated. For example, change in the eye phenotype is a common readout in D. melanogaster, and cell growth rate is a common readout in S. cerevisiae.

Cell type

Various

This field briefly describes what cell lines and organs were utilized to carry out the experiment.