Identified targets

Load list of proteins for prioritization

Out of your selected genes:

P25445, Q13478, Q6UWV6, Q96HD1, Q99988, Q9BZR6

the following targets was matched in our database to the gene names:

FAS, IL18R1, ENPP7, CRELD1, GDF15, RTN4R

1 Functional information

1.1 Target overview

Table

Target overview
	Gene synonyms	Protein name	UniProt ID	Subcellular location	Protein family	Protein class	Target development level
CRELD1	AVSD2, CIRRIN	Protein disulfide isomerase CRELD1, EC 5.3.4.1	Q96HD1	Nucleoli, Cytosol	Non-IDG	Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins	Tbio
ENPP7	alk-SMase, NPP7	Ectonucleotide pyrophosphatase/ phosphodiesterase family member 7, E-NPP 7, NPP-7, EC 3.1.4.12	Q6UWV6	—	Enzyme	Enzymes, Metabolic proteins, Predicted intracellular proteins	Tbio
FAS	APO-1, APT1, CD95, FAS1, TNFRSF6	Tumor necrosis factor receptor superfamily member 6	P25445	Nuclear bodies, Plasma membrane, Cytosol	Non-IDG	Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Predicted secreted proteins	Tbio
GDF15	MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB	Growth/ differentiation factor 15, GDF-15	Q99988	Golgi apparatus	Non-IDG	Cancer-related genes, Disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins	Tbio
IL18R1	CD218a, IL-1Rrp, IL1RRP	Interleukin-18 receptor 1, IL-18R-1, IL-18R1, EC 3.2.2.6	Q13478	Mitochondria	Non-IDG	CD markers, Enzymes, Plasma proteins, Predicted membrane proteins	Tbio
RTN4R	NOGOR	Reticulon-4 receptor	Q9BZR6	Plasma membrane, Actin filaments, Focal adhesion sites	Non-IDG	Disease related genes, Human disease related genes, Predicted membrane proteins	Tbio

About

Table content:

Protein name (UniProt): Name of gene product.
Gene synonyms (HPA): A list of different synonyms (in uppercase) for the (official) gene name provided by HPA.
UniProt ID (UniProt): Link to UniProt for additional information on the target.
Protein class (HPA): Classification of the protein target based on function and cellular compartment and/or disease and drug related information.
Subcellular location (HPA): HPA-assigned subcellular location.
Protein family (PHAROS): Protein family the target is assigned to. Levels: GPCR, Nuclear Receptor, Kinase, Enzyme, Ion Channel, Transcription Factor, Transporter, Epigenetic, oGPCR, TF/Epigenetic, Non-IDG.
Special emphasis is given on four superfamilies that are central to the NIH IDG initiative: GPCRs, kinases, ion channels, and nuclear receptors.
Target development level (PHAROS): Target Development Level (TDL) (for more information on TDL see here). TDL categorizes the target based on known information and potential drugability, with descending ranking:
- Tclin: Approved drugs with known mechanism of action.
- Tchem: If associated with small molecule activities in ChEMBL or DrugCentral.
- Tbio: If not associated with small molecule or drug activities, but have a GO Molecular Function or Biological Process leaf term(s) with an Experimental Evidence code or/and have a confirmed OMIM phenotype.
- Tdark: If not known drug or small molecule activities, and PubMed text-mining score from Jensen Lab <5 or/and ≥3 Gene RIFs or/and ≥50 Antibodies available on http://antibodypedia.com.

em-dash (—) indicates that no information was available for the target.

1.2 Functionality descriptions

Table

Functionality description
	Functionality description	Diabetes associations	Suggested biomarker
CRELD1	Description missing	—	No
ENPP7	Converts sphingomyelin to ceramide and phosphocholine (PubMed:12885774, PubMed:12671034, PubMed:15205117, PubMed:28292932). Has also phospholipase C activity and can cleave phosphocholine from palmitoyl lyso-phosphatidylcholine (PubMed:12885774). Does not have nucleotide pyrophosphatase activity (PubMed:12885774).	—	No
FAS	Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).	T1DM, T2DM, Other	No
GDF15	Regulates food intake, energy expenditure and body weight in response to metabolic and toxin-induced stresses (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:23468844, PubMed:29046435). Binds to its receptor, GFRAL, and activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28953886, PubMed:28846097, PubMed:28846098, PubMed:28846099). It then triggers the activation of neurons localized within the parabrachial nucleus and central amygdala, which contitutes part of the ‘emergency circuit’ that shapes feeding responses to stressful conditions (PubMed:28953886). On hepatocytes, inhibits growth hormone signaling (By similarity).	T1DM, T2DM, GDM, Other	No
IL18R1	Within the IL18 receptor complex, responsible for the binding of the proinflammatory cytokine IL18, but not IL1A nor IL1B (PubMed:8626725, PubMed:14528293, PubMed:25261253, PubMed:25500532). Involved in IL18-mediated IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850). Contributes to IL18-induced cytokine production, either independently of SLC12A3, or as a complex with SLC12A3 (By similarity).	T2DM	No
RTN4R	Receptor for RTN4, OMG and MAG (PubMed:12037567, PubMed:12068310, PubMed:12426574, PubMed:12089450, PubMed:16712417, PubMed:18411262, PubMed:12839991, PubMed:19052207). Functions as receptor for the sialylated gangliosides GT1b and GM1 (PubMed:18411262). Besides, functions as receptor for chondroitin sulfate proteoglycans (By similarity). Can also bind heparin (By similarity). Intracellular signaling cascades are triggered via the coreceptor NGFR (PubMed:12426574). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:16712417, PubMed:22325200). Mediates axonal growth inhibition (PubMed:12839991, PubMed:19052207, PubMed:28892071). Plays a role in regulating axon regeneration and neuronal plasticity in the adult central nervous system. Plays a role in postnatal brain development. Required for normal axon migration across the brain midline and normal formation of the corpus callosum. Protects motoneurons against apoptosis; protection against apoptosis is probably mediated via interaction with MAG. Acts in conjunction with RTN4 and LINGO1 in regulating neuronal precursor cell motility during cortical development. Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200).	T2DM	No

About

Table content:\

Description (PHAROS): Full-text description of the role/function of the protein from PHAROS.
Diabetes associations (Open Targets): Gene-disease (diabetes mellitus) association through experiments or clinical trials. Direct associations with T1DM, T2DM and GDM are shown specifically, while all other diabetes mellitus diseases are included in “Other”.
Suggested biomarker: Known and suggested biomarkers from Abbasi et al, 2016, RHAPSODY partners (collected by the RHAPSODY biomarker taskforce) and based on PPI-network analysis of known biomarkers (in-house analysis).

“Description missing” indicates that no description was available for the target.

2 Experimental evidence

2.1 Volcano plots exploring p-value and effect size relationships

2.1.1 All experimental results for each hit

Plot

Volcano plot - all experiments

About

Individual volcano plots for each target with results from all RHAPSODY experiments plotted.

Shape: Points are shaped according to omics type.
Color: Points with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.

Empty plots indicates that the specific target were not measured in RHAPSODY experiments.

2.1.2 Compare best experimental result for each target based on p-value

Plot

Volcano plot - Best results from each target

Table

Best experimental results for each target by omics-type
	Experiment	Tissue	Comparison	log10 fold change	Adj. p-value
Transcriptomics
CRELD1	IMIDIA	Islets	T2D vs ND	-0.450	1.73e-05
FAS	IMIDIA	Islets	T2D vs ND	0.514	1.42e-04
IL18R1	WP5	Islets LCM	T2D vs ND + Tubingen	1.300	0.058
GDF15	WP6 Mice	Liver	BALBC D05 HF vs RC	-2.114	0.077
RTN4R	WP6 Mice	Adipose tissue	BALBC D33 HF vs RC	1.962	0.126
ENPP7	IMIDIA	Islets	IGT vs ND	0.149	0.363
Proteomics
GDF15	WP3 GoDARTS + DCS	Blood	Cox model 1	0.424	0.030
CRELD1	WP3 GoDARTS + DCS	Blood	Cox model 3	0.382	0.159
ENPP7	WP3 GoDARTS + DCS	Blood	Cox model 3	0.357	0.159
FAS	WP3 GoDARTS + DCS	Blood	Cox model 3	0.315	0.159
IL18R1	WP3 GoDARTS + DCS	Blood	Cox model 1	0.401	0.190
RTN4R	WP3 GoDARTS + DCS	Blood	Cox model 3	0.273	0.430

About

Omics-specific volcano plots with the best result for each tissue based on lowest adjusted p-value. Best results (lowest adjusted p-value) for all targets is shown as background points.

Shape: Points are shaped according to omics type.
Color: Points with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.
Background: The best results for all targets detected in RHAPSODY experiments are included as a reference background in light gray with a reduced size.

The best results from each target is shown in a table format together with the experiment-specific information, including:

Experiment: Experimental setting within the RHAPSODY consortium. Find more information on the experiments here.
Tissue: The tissue the target was detected in. The tissue availability is omics dependent:
- Adipose tissue: Transcriptomics.
- Blood: Proteomics.
- Islets: Transcriptomics.
- Islets LCM (laser capture microdissected): Transcriptomics.
- Liver: Transcriptomics.
- Muscles: Transcriptomics.
Comparison: Experimental setup or modeling.
log10 fold change: log10-transformed fold change (FC).
Adj. p-value: FDR adjusted p-value.

Significant results with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.

2.2 RHAPSODY meta rank

Table

RHAPSODY meta rank
	Detected in blood	Adj. meta p-value	Rank
ENPP7	Yes	1.42e-06	20
CRELD1	Yes	0.008	43
IL18R1	Yes	4.82e-08	94
RTN4R	Yes	0.002	269
GDF15	Yes	2.22e-08	355
FAS	Yes	3.76e-13	538

About

The RHAPSODY meta rank is made to identify novel targets based on RHAPSODY experimental data. The rank is based on three steps:

Meta-analysis of p-values from all transcriptomics and proteomics experiments within the RHAPSODY consortium (see the individual results above). The meta-analysis use the sample size-based meta-analysis described by Willer et al, 2010. The reported meta p-values are FDR-adjusted.
Targets were evaluated on being found in the blood circulation using data from the Human Protein Atlas. Targets found in circulation were included in step 3.
Targets with a significant meta p-value, defined as meta p-value < 0.05, were inversely ranked according to their co-mentions with diabetes. The best rank of 1 was assigned to the lowest number of co-mentions (zero (0) co-mentions), signifying the most novel biomarker for diabetes.

Significant results with an adjusted meta p-value <0.05 are shown in blue, while non-significant points are shown in gray.

em-dash (—) indicates that no information was available for the target.

2.3 Best results within tissue and model

Compare across targets

Compare tissue-specific results across targets

Compare across species

Compare tissue-specific results across species

Rank list table

Best result for each target based on tissue type
		Human		Mouse
	Omics type	log10 fold change	Adj. p-value	log10 fold change	Adj. p-value
Adipose tissue
CRELD1	Transcriptomics	—	—	-1.369	0.084
IL18R1	Transcriptomics	—	—	1.371	0.124
RTN4R	Transcriptomics	—	—	1.962	0.126
FAS	Transcriptomics	—	—	0.399	0.136
ENPP7	Transcriptomics	—	—	2.279	0.654
Blood
GDF15	Proteomics	0.424	0.030	—	—
CRELD1	Proteomics	0.382	0.159	—	—
ENPP7	Proteomics	0.357	0.159	—	—
FAS	Proteomics	0.315	0.159	—	—
IL18R1	Proteomics	0.401	0.190	—	—
RTN4R	Proteomics	0.273	0.430	—	—
Islets
CRELD1	Transcriptomics	-0.450	1.73e-05	0.206	0.212
FAS	Transcriptomics	0.514	1.42e-04	-0.418	0.402
GDF15	Transcriptomics	0.333	0.149	—	—
IL18R1	Transcriptomics	0.238	0.241	—	—
ENPP7	Transcriptomics	0.149	0.363	—	—
Islets LCM
FAS	Transcriptomics	1.092	0.010	—	—
IL18R1	Transcriptomics	1.300	0.058	—	—
GDF15	Transcriptomics	0.683	0.394	—	—
CRELD1	Transcriptomics	-0.129	0.476	—	—
Liver
FAS	Transcriptomics	—	—	0.737	0.006
CRELD1	Transcriptomics	—	—	-0.532	0.026
GDF15	Transcriptomics	—	—	-2.114	0.077
Muscle
FAS	Transcriptomics	—	—	-1.179	0.003
CRELD1	Transcriptomics	—	—	-0.311	0.032

About

Compare across targets

Comparison of targets across tissues and species. The plot is made to enable direct comparison between targets. Dependent on the number of targets, the plot will give target comparisons horizontally (at 8 or fewer targets) or vertically (more than 8 targets).

Line: Connects the best results (lowest adjusted p-value) from each tissue.
Shape: Points are shaped according to omics type.
Color: Points with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.
Color density: Points with a adjusted p-value <0.05 are shown at full density, while points above the p-value threshold are more see-through (lower density).

Empty plots indicates that the specific target were not measured in RHAPSODY experiments.

Compare across species

Comparison of tissues across species for each target. The plot is made to enable direct comparison between tissues and species for each target.

Line: Connects the best results (lowest adjusted p-value) from each tissue.
Shape: Points are shaped according to omics type.
Color: Points with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.
Color density: Points with a adjusted p-value <0.05 are shown at full density, while points above the p-value threshold are more see-through (lower density).

Empty plots indicates that the specific target were not measured in RHAPSODY experiments.

Rank list table

The table summarizes the best results for each tissue and species based on adjusted p-value.

Omics type: Omics type
log10 fold change: log10-transformed fold change (FC).
Adj. p-value: FDR adjusted p-value.

Significant results with an adjusted p-value <0.05 are shown in blue, while non-significant points are shown in gray.

em-dash (—) indicates that no information was available for the target.

3 Disease association

3.1 Text mining results from public and in-house sources

3.1.1 Disease association in scientific articles

Plot

Disease association in scientific articles

About

Text mining results for target-disease (any) association based on in-house and PHAROS data.

In-house text-mining
- UniProt AC - all diseases co-mentions (PubMed): Sum of diabetes and all other diseases co-mentions in PubMed abstracts.
- UniProt AC - all diseases co-mentions (full-text): Sum of diabetes and all other diseases co-mentions in 15 mio full-text articles.
PHAROS
- Jensen Score: Gene-disease association score based on biomedical abstracts, taking co-occurrence within and between sentences into account. Absolute counts are reported here. For more information, see Pletscher-Frankild et al, 2015.
- PubTator Score: Online tool for curation of PubMed articles. Biological entities (chemicals, diseases, genes, mutations, and species) are annotated using entity-specific text-mining tools. Normalized scores used for ranking in the tool is reported here. For more information, see the website and Wei, 2013.

To ease the comparison between the proteins, a geometric mean has been calculated for the five parameters. Geometric means can be calculated with the formula: $GM = \sqrt[n]{x_{1} \cdot x_{2} \cdot ... \cdot x_{n}}$. Using the geometric mean instead of the arithmetic mean (normally known as mean or average) to summarize our data is beneficial for two reasons:

The geometric mean is not affected by the scale of the data. We can therefore summarize our data without normalizing it.
The geometric mean is less sensitive to outliers than the arithmetic mean, but still more sensitive than the median.
The geometric mean is also more stable than the median, which can change dramatically when adding or removing just a few input values if your sample size is small.

However, it is important to note that the geometric mean does not handle zeros and negative values. It is therefore not useful for all data types.

3.1.2 Diabetes fraction of co-mentions

Plot

Disease co-mentions

About

The in-house text-mining has been conducted in two modes for PubMed abstracts and full-text papers:

UniProt AC - all diseases except diabetes co-mentions
UniProt AC - diabetes co-mentions

Using these text-mining results, we can compare the number of co-mentions associated with diabetes to all other diseases.

The plot is split into three panel (left-to-right):

A proportional area plot (left panel) shows the percentage of co-mentions in full text articles that are diabetes-related.
The first bar plot (middle panel) shows the co-mentions count for diabetes in dark blue and the co-mentions count for all diseases but diabetes in light blue derived from 15 million full-text articles (in-house resource, see Westergaard et al. PLoS Computational Biology 2018).
The second bar plot (right panel) shows similar to the middle panel co-mentions count for diabetes in dark blue and the co-mentions count for all diseases but diabetes in light blue. The data is obtained from 15 million abstracts (in-house resource, see Westergaard et al. PLoS Computational Biology 2018).

The plot has been sorted according to highest full-text all diabetes co-mentions.

3.2 Open Targets association scores

Diabetes mellitus (EFO_000400)

Association score for diabetes mellitus (supergroup)

T2DM (MONDO_0005148)

Association score for T2DM

T1DM (MONDO_0005147)

Association score for T1DM

GDM (EFO_0004593)

Association score for GDM

Other diabetes mellitus subtypes

Association score for other diabetes mellitus subtypes

About

Open Targets association scores for the diabetes mellitus supergroup and selected subtypes.

Diabetes mellitus (EFO_0000400): Supergroup for all diabetes mellitus diseases.
T2DM (MONDO_0005148): Type 2 diabetes mellitus.
T1DM (MONDO_0005147): Type 1 diabetes mellitus.
GDM (EFO_0004593): Gestational diabetes mellitus.
Other diabetes mellitus subtypes: Any other diabetes mellitus subgroup than T2DM, T1DM and GDM, e.g., monogenic diabetes mellitus, prediabetes syndrome, and neonatal diabetes mellitus.

The Open Targets association score is a standardized measure reported a value between 0 and 1. Here, 1 indicates a strong association, while 0 indicates that there is no known association. The score is calculated with the formula $s = F \cdot S \cdot C$, where $s$ is the score, $F$ is the frequency i.e. the relative occurrence of a target-disease evidence, $S$ is the severity i.e. the magnitude or strength of the effect described by the evidence, and $C$ is the confidence i.e. overall confidence for the observation that generates the target-disease evidence.
The targets are ranked according to the overall association score, summarizing the seven association variables.

Source: Open Targets Platform Documentation.

4 Mechanistic evidence

4.1 Protein-protein interaction network

4.1.1 Network plots

All interactions

PPI networks

High-confidence interactions only

PPI networks

Summary table

Protein-protein interaction networks summary
Target	Mean diabetes textmining %	Associated with diabetes	Suggested diabetes biomarkers	Potential interaction partners	High-confidence interaction partners	Total interaction partners
CRELD1	—	0	0	0	0	0
ENPP7	15	9	0	20	0	20
FAS	10	71	0	96	21	117
GDF15	10	45	2	67	2	69
IL18R1	13	8	1	8	4	12
RTN4R	9	76	1	191	10	201

About

Protein-protein interaction networks based on physical links data from the STRING database. See Szklarczyk et al, 2018 for a description of the resource.

Network features:

Interaction partners (nodes) are colored according to the confidence score of their interaction with the primary targets.
- High confidence interaction partners (confidence score > 0.7) are shown in blue
- Suggested interaction partners (confidence score ≤ 0.7) are shown in gray
Interactions (edges) are shown according the confidence score of the interaction
- High confidence interactions (confidence score > 0.7) are shown as solid line (—)
- Suggested interactions (confidence score ≤ 0.7) are show as dashed lines (- - -)

Summary table:

Mean diabetes textmining %: The avarage diabetes percentage of diabetes co-mentions to total co-mentions across the network. Based on textmining from Westergaard et al
Associated with diabetes: Number of nodes that have been associated with diabetes mellitus (Open Targets)
Suggested diabetes biomarkers: Number of nodes that have been identified as potential biomarkers for Type 2 diabetes mellitus
Potential interaction partners: Number of interaction partners below the confidence threshold (confidence score ≤ 0.7)
High-confidence interaction partners: Number of interaction partners above the confidence threshold (confidence score > 0.7)
Total interaction partners: Total number of interaction partners

4.1.2 Interaction partners

All interactions

Protein-protein interaction partners
		Diabetes association			Confidence scores for interaction
Interaction partner	UniProt ID	Diabetes textmining %	Diabetes associations	Suggested diabetes biomarker	Experimental score	Database score	Textmining score	Combined score
ENPP7
TTC17	Q96AE7	29	—	No	0.13	0.00	0.26	0.33
ACER2	Q5QJU3	22	—	No	0.00	0.65	0.00	0.65
ASAH2	Q9NR71	19	T2DM	No	0.00	0.65	0.00	0.65
CERS6	Q6ZMG9	19	T2DM	No	0.00	0.65	0.00	0.65
PIGF	Q07326	18	—	No	0.08	0.00	0.14	0.18
CERS4	Q9HA82	17	T2DM	No	0.00	0.65	0.00	0.65
SGPP1	Q9BX95	17	T2DM	No	0.00	0.65	0.00	0.65
CERS2	Q96G23	17	T1DM, T2DM	No	0.00	0.65	0.00	0.65
ACER1	Q8TDN7	16	—	No	0.00	0.65	0.00	0.65
CERS3	Q8IU89	16	—	No	0.00	0.65	0.00	0.65
PLPP3	O14495	15	—	No	0.00	0.65	0.00	0.65
SGPP2	Q8IWX5	14	Other	No	0.00	0.65	0.00	0.65
PLPP2	O43688	14	—	No	0.00	0.65	0.00	0.65
ASAH1	Q13510	13	T1DM, T2DM, GDM, Other	No	0.00	0.65	0.00	0.65
GBA2	Q9HCG7	11	T2DM	No	0.00	0.65	0.00	0.65
DEGS2	Q6QHC5	11	—	No	0.00	0.65	0.00	0.65
DEGS1	O15121	10	T1DM, T2DM	No	0.00	0.65	0.00	0.65
GBA	P04062	9	—	No	0.00	0.65	0.00	0.65
LRRC73	Q5JTD7	—	—	No	0.26	0.00	0.00	0.26
CERS5	Q8N5B7	—	—	No	0.00	0.65	0.00	0.65
FAS
SFXN5	Q8TD22	23	—	No	0.22	0.00	0.00	0.22
TNFRSF10A	O00220	22	T1DM, T2DM, GDM	No	0.00	0.60	0.42	0.76
GGCX	P38435	22	—	No	0.00	0.00	0.34	0.34
UFSP2	Q9NUQ7	22	—	No	0.22	0.00	0.00	0.22
SPATA5L1	Q9BVQ7	22	—	No	0.21	0.00	0.00	0.21
ACAD9	Q9H845	21	—	No	0.16	0.00	0.00	0.16
NDUFAF1	Q9Y375	20	T1DM, T2DM, GDM, Other	No	0.19	0.00	0.00	0.19
PEX1	O43933	18	Other	No	0.27	0.00	0.00	0.27
MAP3K5	Q99683	17	T1DM, T2DM	No	0.64	0.90	0.00	0.96
PEA15	Q15121	17	T2DM	No	0.28	0.00	0.00	0.28
HNF4A	P41235	17	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.26	0.26
PDXDC1	Q6P996	17	T2DM	No	0.22	0.00	0.00	0.22
CAV1	Q03135	16	T1DM, T2DM, GDM, Other	No	0.48	0.00	0.46	0.71
HSPA5	P11021	16	T1DM, T2DM, GDM, Other	No	0.27	0.00	0.00	0.27
MAPK8	P45983	15	T1DM, T2DM, GDM, Other	No	0.64	0.00	0.00	0.64
TRAF2	Q12933	15	—	No	0.00	0.60	0.00	0.60
LGALS3	P17931	15	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.33	0.33
PIK3R1	P27986	15	T1DM, T2DM, GDM, Other	No	0.27	0.00	0.00	0.27
ATG5	Q9H1Y0	14	T2DM, Other	No	0.48	0.00	0.25	0.59
CD40	P25942	14	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.53	0.53
TNFSF13	O75888	14	—	No	0.27	0.00	0.00	0.27
LTA	P01374	14	T1DM, T2DM, GDM, Other	No	0.06	0.00	0.19	0.20
C1QC	P02747	14	—	No	0.00	0.00	0.18	0.18
TNFRSF1A	P19438	13	T1DM, T2DM, GDM, Other	No	0.29	0.00	0.40	0.55
WDR11	Q9BZH6	13	T2DM, Other	No	0.42	0.00	0.00	0.42
MAP1LC3B	Q9GZQ8	13	T2DM	No	0.27	0.00	0.00	0.27
PSTPIP1	O43586	13	T2DM	No	0.00	0.00	0.25	0.25
C1QA	P02745	13	—	No	0.00	0.00	0.18	0.18
FASLG	P48023	12	T1DM, T2DM, Other	No	0.65	0.90	0.90	1.00
FAF1	Q9UNN5	12	T2DM	No	0.50	0.90	0.45	0.97
SQSTM1	Q13501	12	T1DM, T2DM, Other	No	0.27	0.00	0.00	0.27
ANK3	Q12955	12	T1DM	No	0.21	0.00	0.00	0.21
NRP1	O14786	12	T1DM, T2DM	No	0.00	0.00	0.16	0.16
TNFRSF10B	O14763	11	T1DM, T2DM	No	0.29	0.60	0.00	0.70
PLCG1	P19174	11	T2DM	No	0.27	0.00	0.61	0.70
RHOA	P61586	11	T1DM, T2DM, Other	No	0.65	0.00	0.00	0.65
HIPK3	Q9H422	11	T2DM, Other	No	0.34	0.00	0.28	0.50
TRAF3	Q13114	11	T2DM	No	0.27	0.00	0.00	0.27
CANX	P27824	11	—	No	0.00	0.00	0.25	0.25
ARF5	P84085	11	T2DM	No	0.24	0.00	0.00	0.24
GPD1L	Q8N335	11	—	No	0.20	0.00	0.00	0.20
UNC5B	Q8IZJ1	11	GDM	No	0.00	0.00	0.18	0.18
RIPK1	Q13546	10	—	No	0.44	0.90	0.47	0.97
CASP10	Q92851	10	—	No	0.52	0.90	0.47	0.97
FAIM2	Q9BWQ8	10	T2DM, GDM	No	0.27	0.90	0.00	0.92
PTPN13	Q12923	10	—	No	0.48	0.00	0.41	0.68
TNFSF10	P50591	10	T1DM, T2DM	No	0.00	0.60	0.00	0.60
FYN	P06241	10	T2DM, GDM	No	0.50	0.00	0.00	0.50
LCK	P06239	10	T1DM	No	0.48	0.00	0.00	0.48
HSPA8	P11142	10	—	No	0.00	0.00	0.43	0.43
CTNNB1	P35222	10	T1DM, T2DM, GDM	No	0.39	0.00	0.00	0.39
CASP3	P42574	10	T1DM, T2DM, GDM, Other	No	0.06	0.36	0.00	0.37
TUBB4A	P04350	10	Other	No	0.28	0.00	0.00	0.28
HSPA4	P34932	10	—	No	0.00	0.00	0.27	0.27
EIF2AK3	Q9NZJ5	10	T1DM, T2DM, GDM, Other	No	0.27	0.00	0.00	0.27
FCGR2B	P31994	10	T2DM, Other	No	0.00	0.00	0.23	0.23
CDYL	Q9Y232	10	—	No	0.22	0.00	0.00	0.22
TUBB2B	Q9BVA1	10	—	No	0.21	0.00	0.00	0.21
UGDH	O60701	10	—	No	0.19	0.00	0.00	0.19
CFLAR	O15519	9	T2DM	No	0.49	0.90	0.45	0.97
SRC	P12931	9	T1DM, T2DM	No	0.48	0.90	0.20	0.95
BTK	Q06187	9	—	No	0.00	0.90	0.07	0.90
SYK	P43405	9	Other	No	0.00	0.90	0.00	0.90
SUMO1	P63165	9	T1DM, T2DM	No	0.48	0.00	0.61	0.79
BID	P55957	9	T1DM	No	0.65	0.00	0.00	0.65
RAP1A	P62834	9	T2DM, GDM	No	0.55	0.00	0.00	0.55
UBE2I	P63279	9	T2DM	No	0.50	0.00	0.00	0.50
HIPK2	Q9H2X6	9	—	No	0.10	0.00	0.41	0.45
TRIP6	Q15654	9	—	No	0.27	0.00	0.00	0.27
CD44	P16070	9	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.26	0.25
TUBB2A	Q13885	9	—	No	0.21	0.00	0.00	0.21
CASP8	Q14790	8	T1DM, T2DM	No	0.53	0.90	0.94	1.00
FADD	Q13158	8	T1DM	No	0.95	0.90	0.91	1.00
YES1	P07947	8	—	No	0.48	0.00	0.00	0.48
BMP1	P13497	8	—	No	0.00	0.00	0.29	0.29
APAF1	O14727	8	—	No	0.25	0.00	0.00	0.24
RUFY1	Q96T51	8	T2DM	No	0.23	0.00	0.00	0.23
EGFR	P00533	7	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.75	0.75
EZR	P15311	7	T1DM	No	0.47	0.00	0.16	0.54
FEM1B	Q9UK73	7	T1DM, T2DM, Other	No	0.21	0.00	0.28	0.41
PML	P29590	7	T1DM, T2DM	No	0.34	0.00	0.00	0.34
MSN	P26038	7	T2DM	No	0.30	0.00	0.00	0.30
ARHGDIA	P52565	7	T1DM, Other	No	0.29	0.00	0.00	0.29
RARA	P10276	7	T2DM	No	0.27	0.00	0.00	0.27
IFNB1	P01574	7	T1DM, T2DM, Other	No	0.00	0.00	0.26	0.26
RHOBTB3	O94955	7	—	No	0.22	0.00	0.00	0.22
LYN	P07948	7	T1DM, T2DM, Other	No	0.00	0.00	0.22	0.22
UBA7	P41226	7	T2DM	No	0.21	0.00	0.00	0.21
FAF2	Q96CS3	7	—	No	0.20	0.00	0.00	0.20
KRIT1	O00522	6	—	No	0.27	0.00	0.00	0.27
TUBB3	Q13509	6	—	No	0.24	0.00	0.00	0.24
DPH1	Q9BZG8	6	—	No	0.23	0.00	0.00	0.23
RDX	P35241	6	T1DM, T2DM	No	0.06	0.00	0.20	0.21
FBF1	Q8TES7	6	Other	No	0.19	0.00	0.00	0.19
C17orf75	Q9HAS0	5	—	No	0.63	0.00	0.00	0.63
PLK3	Q9H4B4	5	—	No	0.00	0.00	0.40	0.40
PRAM1	Q96QH2	5	—	No	0.27	0.00	0.00	0.27
PDCD6	O75340	5	—	No	0.27	0.00	0.00	0.27
PLK1	P53350	5	T2DM, GDM	No	0.00	0.00	0.20	0.20
MAP1S	Q66K74	5	—	No	0.19	0.00	0.00	0.19
INPP5D	Q92835	4	T1DM, T2DM	No	0.27	0.00	0.25	0.43
TP63	Q9H3D4	4	—	No	0.27	0.00	0.00	0.27
EEF1AKNMT	Q8N6R0	4	—	No	0.21	0.00	0.00	0.21
INTS2	Q9H0H0	4	—	No	0.19	0.00	0.00	0.19
BABAM2	Q9NXR7	3	—	No	0.27	0.00	0.00	0.27
CTU2	Q2VPK5	3	—	No	0.24	0.00	0.00	0.24
FAM91A1	Q658Y4	—	—	No	0.41	0.00	0.00	0.41
FAM118B	Q9BPY3	—	—	No	0.23	0.00	0.00	0.23
TIMM29	Q9BSF4	—	—	No	0.23	0.00	0.00	0.23
DAXX	Q9UER7	—	T1DM	No	0.66	0.90	0.39	0.98
TRADD	Q15628	—	—	No	0.46	0.90	0.28	0.96
CALM1	P0DP23	—	T1DM, GDM	No	0.80	0.00	0.00	0.80
PRKCA	P17252	—	T1DM, T2DM	No	0.55	0.00	0.00	0.55
TNF	P01375	—	T1DM, T2DM, GDM, Other	No	0.28	0.00	0.19	0.39
ABHD11	Q8NFV4	—	Other	No	0.39	0.00	0.00	0.39
CASP8AP2	Q9UKL3	—	—	No	0.34	0.00	0.00	0.34
CHD1L	Q86WJ1	—	T2DM	No	0.21	0.00	0.00	0.21
GDF15
INSR	P06213	27	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.08	0.18
ERN1	O75460	26	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.07	0.17
PRKCZ	Q05513	23	T2DM, GDM	No	0.15	0.00	0.05	0.16
GSK3A	P49840	22	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.06	0.16
IGF1R	P08069	17	T1DM, T2DM, GDM, Other	RHAPSODY partner suggestion	0.15	0.00	0.08	0.18
IRAK3	Q9Y616	16	T1DM, T2DM	No	0.15	0.00	0.05	0.16
GSK3B	P49841	15	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.08	0.18
STAT5A	P42229	14	T1DM, T2DM, GDM	No	0.25	0.00	0.00	0.25
ACVR1C	Q8NER5	14	T2DM	No	0.15	0.00	0.05	0.16
PRKCI	P41743	14	—	No	0.15	0.00	0.05	0.16
SETD4	Q9NVD3	13	Other	No	0.26	0.00	0.00	0.26
MAP3K11	Q16584	13	—	No	0.15	0.00	0.08	0.18
IRAK4	Q9NWZ3	13	T2DM	No	0.15	0.00	0.05	0.16
ACVRL1	P37023	12	—	No	0.15	0.00	0.30	0.38
CDC42BPG	Q6DT37	12	—	No	0.15	0.00	0.14	0.23
CDC42BPB	Q9Y5S2	12	—	No	0.15	0.00	0.08	0.18
MAP3K21	Q5TCX8	12	—	No	0.15	0.00	0.08	0.18
ROCK1	Q13464	12	T1DM, T2DM	No	0.15	0.00	0.08	0.18
CCN3	P48745	12	T2DM	Network expansion	0.00	0.00	0.17	0.17
ACVR2A	P27037	12	—	No	0.15	0.00	0.06	0.16
IRAK1	P51617	12	T1DM, T2DM	No	0.15	0.00	0.05	0.16
MAP3K9	P80192	11	—	No	0.15	0.00	0.11	0.21
ROCK2	O75116	11	T1DM, T2DM	No	0.15	0.00	0.08	0.18
MAP3K10	Q02779	11	—	No	0.15	0.00	0.08	0.18
COL12A1	Q99715	11	—	No	0.08	0.00	0.14	0.17
RIPK3	Q9Y572	11	T1DM, T2DM	No	0.15	0.00	0.07	0.17
ACVR1B	P36896	11	—	No	0.15	0.00	0.05	0.16
LIMK2	P53671	11	—	No	0.15	0.00	0.05	0.16
PASK	Q96RG2	11	T2DM, Other	No	0.15	0.00	0.04	0.15
BMPR1A	P36894	10	T2DM	No	0.15	0.00	0.10	0.20
AXL	P30530	10	T1DM, T2DM	No	0.15	0.00	0.08	0.18
IRAK2	O43187	10	T2DM	No	0.15	0.00	0.05	0.16
NTRK1	P04629	10	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.05	0.16
ERN2	Q76MJ5	10	—	No	0.15	0.00	0.06	0.16
TGFBR2	P37173	9	T1DM, T2DM	No	0.15	0.00	0.42	0.49
NTRK2	Q16620	9	T1DM, T2DM, Other	No	0.15	0.00	0.08	0.18
RIPK2	O43353	9	T2DM	No	0.15	0.00	0.08	0.18
BMPR1B	O00238	9	T2DM	No	0.15	0.00	0.07	0.17
GDNF	P39905	9	T1DM, T2DM, Other	No	0.00	0.00	0.16	0.16
PTK7	Q13308	9	—	No	0.15	0.00	0.04	0.15
LRRK2	Q5S007	9	T1DM, T2DM, Other	No	0.15	0.00	0.05	0.15
SAE1	Q9UBE0	8	T2DM	No	0.21	0.00	0.00	0.21
CDC42BPA	Q5VT25	8	—	No	0.15	0.00	0.08	0.18
NTRK3	Q16288	8	—	No	0.15	0.00	0.08	0.18
PTK6	Q13882	8	—	No	0.15	0.00	0.06	0.17
MET	P08581	8	T1DM, T2DM, GDM, Other	No	0.15	0.00	0.05	0.16
MERTK	Q12866	8	T2DM, Other	No	0.15	0.00	0.06	0.16
TWSG1	Q9GZX9	7	T1DM	No	0.10	0.00	0.65	0.67
VIM	P08670	7	T1DM, T2DM, Other	No	0.14	0.00	0.27	0.34
GFRA1	P56159	7	—	No	0.00	0.00	0.27	0.27
ABL2	P42684	7	T2DM	No	0.15	0.00	0.08	0.18
ALK	Q9UM73	7	T1DM, Other	No	0.15	0.00	0.06	0.17
MDM2	Q00987	6	T1DM, T2DM	No	0.00	0.00	0.25	0.25
NUP58	Q9BVL2	6	T1DM	No	0.21	0.00	0.00	0.21
NLGN3	Q9NZ94	6	T2DM	No	0.19	0.00	0.00	0.19
FES	P07332	6	—	No	0.15	0.00	0.05	0.16
PKDCC	Q504Y2	6	—	No	0.15	0.00	0.05	0.16
RET	P07949	5	T1DM, T2DM, Other	No	0.80	0.00	0.27	0.85
ENG	P17813	5	T1DM, T2DM, Other	No	0.27	0.00	0.00	0.27
CIT	O14578	5	—	No	0.15	0.00	0.08	0.18
ROS1	P08922	5	T2DM	No	0.15	0.00	0.05	0.16
GFRAL	Q6UXV0	4	T2DM	No	0.80	0.00	0.90	0.98
MDFI	Q99750	4	—	No	0.28	0.00	0.00	0.28
CBX3	Q13185	4	—	No	0.27	0.00	0.00	0.27
INSRR	P14616	4	T2DM	No	0.15	0.00	0.08	0.18
MST1R	Q04912	3	T2DM	No	0.15	0.00	0.05	0.16
FER	P16591	3	Other	No	0.15	0.00	0.05	0.16
CCN2	P29279	—	T1DM, T2DM, Other	No	0.00	0.00	0.28	0.28
LIMK1	P53667	—	—	No	0.15	0.00	0.05	0.16
IL18R1
SCT	P09683	21	T1DM, T2DM	No	0.00	0.00	0.28	0.28
IL18	Q14116	19	T1DM, T2DM, GDM, Other	Abbasi et al, 2016	0.93	0.90	0.91	1.00
IL33	O95760	15	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.54	0.54
IL37	Q9NZH6	13	T1DM, T2DM, GDM	No	0.28	0.60	0.78	0.93
IL18RAP	O95256	12	T1DM	No	0.80	0.90	0.91	1.00
SIGIRR	Q6IA17	12	—	No	0.00	0.60	0.60	0.84
IRAK1	P51617	12	T1DM, T2DM	No	0.05	0.00	0.19	0.19
SLC12A3	P55017	12	T1DM, T2DM	No	0.18	0.00	0.00	0.18
TICAM2	Q86XR7	11	—	No	0.00	0.00	0.21	0.21
DNMT3A	Q9Y6K1	10	T1DM, T2DM, GDM	No	0.00	0.00	0.43	0.43
IL1RAPL1	Q9NZN1	8	—	No	0.00	0.00	0.56	0.56
RTN4R
BUD13	Q9BRD0	31	—	No	0.17	0.00	0.00	0.17
CAB39	Q9Y376	23	—	No	0.17	0.00	0.11	0.23
CISD3	P0C7P0	23	—	No	0.17	0.00	0.00	0.17
SORT1	Q99523	20	T2DM, Other	No	0.00	0.00	0.38	0.38
MRPS16	Q9Y3D3	20	—	No	0.17	0.00	0.00	0.17
SLC25A10	Q9UBX3	20	—	No	0.16	0.00	0.00	0.16
RPL3L	Q92901	20	—	No	0.17	0.00	0.00	0.16
SNAPC4	Q5SXM2	19	T1DM, T2DM	No	0.16	0.00	0.00	0.16
PTPRQ	Q9UMZ3	18	—	No	0.27	0.00	0.00	0.27
MRPL33	O75394	18	T1DM	No	0.17	0.00	0.00	0.17
CTH	P32929	17	T1DM, T2DM	No	0.00	0.00	0.25	0.25
TNFRSF1B	P20333	17	T1DM, T2DM, GDM	Abbasi et al, 2016	0.00	0.00	0.21	0.21
PTPRA	P18433	17	—	No	0.18	0.00	0.00	0.18
STK25	O00506	17	T1DM, T2DM	No	0.17	0.00	0.00	0.17
CAB39L	Q9H9S4	16	—	No	0.17	0.00	0.11	0.23
PTPRE	P23469	16	—	No	0.18	0.00	0.00	0.18
NWD1	Q149M9	16	—	No	0.18	0.00	0.00	0.18
NRXN3	Q9Y4C0	16	T2DM	No	0.18	0.00	0.00	0.18
FXN	Q16595	16	T2DM	No	0.17	0.00	0.00	0.17
MRPS5	P82675	16	—	No	0.17	0.00	0.00	0.17
MRPL12	P52815	16	—	No	0.16	0.00	0.00	0.16
SNRPN	P63162	16	—	No	0.15	0.00	0.00	0.15
SUOX	P51687	15	T1DM, T2DM	No	0.19	0.00	0.00	0.19
PTPRT	O14522	15	—	No	0.18	0.00	0.00	0.18
USHBP1	Q8N6Y0	15	—	No	0.17	0.00	0.00	0.17
MRPL21	Q7Z2W9	15	—	No	0.17	0.00	0.00	0.17
MRPL4	Q9BYD3	15	—	No	0.16	0.00	0.00	0.16
MT-ND1	P03886	14	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.61	0.61
LTA	P01374	14	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.44	0.44
ZMAT5	Q9UDW3	14	T2DM	No	0.17	0.00	0.00	0.17
S1PR2	O95136	13	T2DM	No	0.00	0.00	0.37	0.37
KDR	P35968	13	T1DM, T2DM, GDM	No	0.08	0.00	0.26	0.29
LY86	O95711	13	Other	No	0.20	0.00	0.00	0.20
PTPRD	P23468	13	T2DM, GDM	No	0.18	0.00	0.00	0.18
SNRPB2	P08579	13	—	No	0.18	0.00	0.00	0.18
SART1	O43290	13	—	No	0.17	0.00	0.00	0.17
PPP1CC	P36873	13	—	No	0.16	0.00	0.05	0.16
PPP1CB	P62140	13	T1DM, T2DM	No	0.16	0.00	0.05	0.16
PPP3CB	P16298	13	—	No	0.16	0.00	0.05	0.16
RNPC3	Q96LT9	12	T2DM	No	0.18	0.00	0.00	0.18
PTPRS	Q13332	12	T1DM	No	0.18	0.00	0.00	0.18
STK24	Q9Y6E0	12	—	No	0.17	0.00	0.00	0.17
LSM8	O95777	12	—	No	0.17	0.00	0.00	0.17
PPP3CC	P48454	12	—	No	0.16	0.00	0.05	0.16
PPP2CA	P67775	12	T2DM	No	0.16	0.00	0.05	0.16
SNRPD1	P62314	12	—	No	0.15	0.00	0.00	0.15
MSRB3	Q8IXL7	12	—	No	0.15	0.00	0.00	0.15
MSRB2	Q9Y3D2	12	—	No	0.15	0.00	0.00	0.15
ACTB	P60709	11	T1DM, T2DM, GDM, Other	No	0.10	0.00	0.31	0.35
ITGB1	P05556	11	T1DM, T2DM, GDM	No	0.04	0.00	0.23	0.24
BUD31	P41223	11	—	No	0.21	0.00	0.00	0.21
SNRPG	P62308	11	—	No	0.21	0.00	0.00	0.21
PRPF39	Q86UA1	11	T1DM	No	0.17	0.00	0.06	0.19
PTPRK	Q15262	11	T1DM	No	0.18	0.00	0.00	0.18
GFM1	Q96RP9	11	—	No	0.17	0.00	0.00	0.17
MRPL27	Q9P0M9	11	—	No	0.17	0.00	0.00	0.17
CWF19L2	Q2TBE0	11	—	No	0.17	0.00	0.00	0.17
MYBL1	P10243	11	—	No	0.16	0.00	0.00	0.16
POTEF	A5A3E0	11	—	No	0.10	0.00	0.10	0.15
IFNG	P01579	10	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.35	0.34
PTPRC	P08575	10	T1DM, T2DM, GDM	No	0.18	0.00	0.09	0.22
ITGAV	P06756	10	T1DM, GDM	No	0.00	0.00	0.20	0.20
MRPL17	Q9NRX2	10	—	No	0.17	0.00	0.00	0.17
NTN5	Q8WTR8	10	T1DM	No	0.17	0.00	0.00	0.17
CTNNB1	P35222	10	T1DM, T2DM, GDM	No	0.06	0.00	0.14	0.16
PPEF2	O14830	10	—	No	0.16	0.00	0.05	0.16
ANPEP	P15144	9	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.90	0.90
APP	P05067	9	T1DM, T2DM, GDM, Other	No	0.05	0.00	0.84	0.84
ROBO2	Q9HCK4	9	T2DM	No	0.13	0.00	0.19	0.27
IL20RA	Q9UHF4	9	T2DM	No	0.00	0.00	0.25	0.25
MYOC	Q99972	9	—	No	0.06	0.00	0.23	0.24
CNTNAP1	P78357	9	T2DM	No	0.00	0.00	0.19	0.19
SNRPA	P09012	9	—	No	0.18	0.00	0.00	0.18
EFL1	Q7Z2Z2	9	—	No	0.17	0.00	0.00	0.17
EEF2	P13639	9	—	No	0.17	0.00	0.00	0.17
PPP5C	P53041	9	—	No	0.16	0.00	0.05	0.16
NAA38	Q9BRA0	9	—	No	0.15	0.00	0.00	0.15
POTEI	P0CG38	9	—	No	0.10	0.00	0.10	0.15
LSM6	P62312	9	—	No	0.15	0.00	0.00	0.15
RHO	P08100	9	T1DM, T2DM	No	0.00	0.00	0.15	0.15
NGFR	P08138	8	T1DM, T2DM	No	0.50	0.90	0.90	0.99
MAG	P20916	8	—	No	0.24	0.90	0.73	0.98
LILRB3	O75022	8	—	No	0.00	0.00	0.42	0.42
RTN1	Q16799	8	—	No	0.17	0.00	0.31	0.41
ADAM22	Q9P0K1	8	T1DM	No	0.00	0.00	0.36	0.36
PLRG1	O43660	8	—	No	0.21	0.00	0.00	0.21
SF3B3	Q15393	8	—	No	0.21	0.00	0.00	0.21
OLFM1	Q99784	8	—	No	0.06	0.00	0.19	0.20
NTN1	O95631	8	T1DM, T2DM, GDM	No	0.17	0.00	0.07	0.19
FGFR1	P11362	8	T1DM, T2DM	No	0.18	0.00	0.00	0.17
LSM7	Q9UK45	8	—	No	0.17	0.00	0.00	0.17
STK26	Q9P289	8	Other	No	0.17	0.00	0.00	0.17
SRRM2	Q9UQ35	8	T2DM	No	0.17	0.00	0.00	0.17
PPP3CA	Q08209	8	Other	No	0.16	0.00	0.05	0.16
TTF1	Q15361	8	—	No	0.16	0.00	0.00	0.16
PPP4C	P60510	8	T1DM	No	0.16	0.00	0.05	0.16
MYB	P10242	8	T2DM, Other	No	0.16	0.00	0.00	0.16
PPP2CB	P62714	8	—	No	0.16	0.00	0.05	0.16
SNRPD2	P62316	8	T2DM	No	0.15	0.00	0.00	0.15
SNRPB	P14678	8	—	No	0.15	0.00	0.00	0.15
SNIP1	Q8TAD8	8	—	No	0.15	0.00	0.00	0.15
ARHGDIA	P52565	7	T1DM, Other	No	0.00	0.90	0.00	0.90
RBM25	P49756	7	—	No	0.35	0.00	0.00	0.35
SNRPF	P62306	7	—	No	0.22	0.00	0.00	0.22
SNW1	Q13573	7	—	No	0.21	0.00	0.00	0.21
XAB2	Q9HCS7	7	GDM	No	0.18	0.00	0.06	0.20
ROBO1	Q9Y6N7	7	—	No	0.13	0.00	0.11	0.19
SF3B5	Q9BWJ5	7	—	No	0.18	0.00	0.00	0.18
ASCC3	Q8N3C0	7	—	No	0.17	0.00	0.00	0.17
MAP3K8	P41279	7	T2DM	No	0.17	0.00	0.00	0.17
CWC22	Q9HCG8	7	T1DM	No	0.17	0.00	0.00	0.17
CWC25	Q9NXE8	7	—	No	0.17	0.00	0.00	0.17
MRPL20	Q9BYC9	7	—	No	0.17	0.00	0.00	0.17
PPP1CA	P62136	7	—	No	0.16	0.00	0.05	0.16
LSM3	P62310	7	—	No	0.16	0.00	0.00	0.16
PPEF1	O14829	7	—	No	0.16	0.00	0.05	0.16
CNTN1	Q12860	7	T1DM	No	0.08	0.00	0.12	0.15
LSM5	Q9Y4Y9	7	—	No	0.15	0.00	0.00	0.15
EGFR	P00533	7	T1DM, T2DM, GDM, Other	No	0.07	0.00	0.12	0.15
SNRPD3	P62318	7	—	No	0.15	0.00	0.00	0.15
MSRB1	Q9NZV6	7	—	No	0.15	0.00	0.00	0.15
RTN4	Q9NQC3	6	T2DM	No	0.24	0.90	0.90	0.99
KIAA0319L	Q8IZA0	6	T1DM	No	0.27	0.00	0.47	0.59
TNFSF13B	Q9Y275	6	T1DM, T2DM, GDM	No	0.00	0.00	0.44	0.44
PRPF19	Q9UMS4	6	—	No	0.22	0.00	0.00	0.22
SF3A3	Q12874	6	T1DM	No	0.20	0.00	0.00	0.20
HEATR6	Q6AI08	6	—	No	0.18	0.00	0.06	0.20
NTNG1	Q9Y2I2	6	—	No	0.20	0.00	0.00	0.20
TFIP11	Q9UBB9	6	—	No	0.18	0.00	0.00	0.18
PTPRU	Q92729	6	—	No	0.18	0.00	0.00	0.18
NRXN2	Q9P2S2	6	—	No	0.18	0.00	0.00	0.18
NTNG2	Q96CW9	6	T2DM	No	0.17	0.00	0.00	0.17
RPS2	P15880	6	—	No	0.17	0.00	0.00	0.17
NTN3	O00634	6	—	No	0.17	0.00	0.00	0.17
EFTUD2	Q15029	6	—	No	0.17	0.00	0.00	0.17
MRPS9	P82933	6	T2DM	No	0.17	0.00	0.00	0.17
PRPF6	O94906	6	T1DM	No	0.17	0.00	0.00	0.17
RPL4	P36578	6	—	No	0.16	0.00	0.00	0.16
DMTF1	Q9Y222	6	—	No	0.16	0.00	0.00	0.16
SLU7	O95391	6	T1DM	No	0.15	0.00	0.00	0.15
LINGO1	Q96FE5	5	T2DM	No	0.48	0.90	0.90	0.99
OMG	P23515	5	T2DM	No	0.30	0.90	0.90	0.99
LGI1	O95970	5	Other	No	0.00	0.00	0.29	0.29
RTN4RL1	Q86UN2	5	—	No	0.00	0.00	0.29	0.29
MYCN	P04198	5	T2DM	No	0.00	0.00	0.26	0.26
PRPF40B	Q6NWY9	5	—	No	0.24	0.00	0.00	0.24
SF3B2	Q13435	5	—	No	0.21	0.00	0.06	0.23
RBM22	Q9NW64	5	—	No	0.21	0.00	0.00	0.21
CCDC130	P13994	5	—	No	0.18	0.00	0.00	0.18
PTPRM	P28827	5	T2DM	No	0.18	0.00	0.00	0.18
HFM1	A2PYH4	5	T1DM, T2DM	No	0.17	0.00	0.00	0.17
PPT1	P50897	5	—	No	0.16	0.00	0.00	0.16
RPL3	P39023	5	—	No	0.17	0.00	0.00	0.16
MYBL2	P10244	5	T2DM	No	0.16	0.00	0.00	0.16
MRPL3	P09001	5	T2DM	No	0.17	0.00	0.00	0.16
CDC5L	Q99459	5	—	No	0.16	0.00	0.00	0.16
RPS16	P62249	5	—	No	0.16	0.00	0.00	0.16
SNRPE	P62304	5	—	No	0.15	0.00	0.00	0.15
POTEE	Q6S8J3	5	—	No	0.10	0.00	0.10	0.15
LSM10	Q969L4	5	—	No	0.15	0.00	0.00	0.15
PRPF8	Q6P2Q9	4	—	No	0.21	0.00	0.00	0.21
CDC40	O60508	4	—	No	0.18	0.00	0.00	0.18
PTPRF	P10586	4	T2DM	No	0.18	0.00	0.00	0.18
SF3A1	Q15459	4	—	No	0.18	0.00	0.00	0.18
LSM4	Q9Y4Z0	4	—	No	0.17	0.00	0.00	0.17
AQR	O60306	4	T2DM	No	0.17	0.00	0.00	0.17
SNRPC	P09234	4	—	No	0.17	0.00	0.00	0.17
RBMX2	Q9Y388	4	—	No	0.15	0.00	0.00	0.15
TNFRSF19	Q9NS68	3	—	No	0.00	0.00	0.88	0.88
RHOH	Q15669	3	—	No	0.10	0.00	0.61	0.64
RTN4RL2	Q86UN3	3	—	No	0.00	0.00	0.27	0.27
ROBO3	Q96MS0	3	—	No	0.13	0.00	0.14	0.22
CRNKL1	Q9BZJ0	3	—	No	0.21	0.00	0.00	0.21
SYF2	O95926	3	—	No	0.21	0.00	0.00	0.21
BCAS2	O75934	3	—	No	0.18	0.00	0.00	0.18
SF3A2	Q15428	3	—	No	0.18	0.00	0.00	0.18
SNRNP200	O75643	3	—	No	0.17	0.00	0.00	0.17
PPP1R42	Q7Z4L9	3	—	No	0.16	0.00	0.00	0.16
SNRNP40	Q96DI7	3	—	No	0.16	0.00	0.00	0.16
DAW1	Q8N136	3	—	No	0.16	0.00	0.00	0.16
SF3B1	O75533	2	—	No	0.21	0.00	0.00	0.21
WDR25	Q64LD2	—	—	No	0.18	0.00	0.00	0.18
GPATCH8	Q9UKJ3	—	—	No	0.18	0.00	0.00	0.18
ISY1	Q9ULR0	—	—	No	0.18	0.00	0.00	0.18
YJU2	Q9BW85	—	—	No	0.18	0.00	0.00	0.18
ZMAT2	Q96NC0	—	—	No	0.17	0.00	0.00	0.17
PRPF4	O43172	—	—	No	0.16	0.00	0.00	0.16
PPP5D1	E7EU14	—	—	No	0.16	0.00	0.05	0.16
POTEJ	P0CG39	—	—	No	0.10	0.00	0.10	0.15
TNF	P01375	—	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.88	0.88
MOG	Q16653	—	T1DM, Other	No	0.00	0.00	0.34	0.34
PPP1R11	O60927	—	T1DM	No	0.18	0.00	0.08	0.22
CWC15	Q9P013	—	—	No	0.21	0.00	0.00	0.21
SF3B4	Q15427	—	T2DM	No	0.18	0.00	0.00	0.18
NRXN1	Q9ULB1	—	T1DM	No	0.18	0.00	0.00	0.18
SRRM3	A6NNA2	—	—	No	0.17	0.00	0.00	0.17
PPT2	Q9UMR5	—	T2DM	No	0.16	0.00	0.00	0.16
PRPF3	O43395	—	T1DM	No	0.16	0.00	0.00	0.16
LSM2	Q9Y333	—	—	No	0.15	0.00	0.00	0.15

High-confidence interactions only

Protein-protein interaction partners
		Diabetes association			Confidence scores for interaction
Interaction partner	UniProt ID	Diabetes textmining %	Diabetes associations	Suggested diabetes biomarker	Experimental score	Database score	Textmining score	Combined score
FAS
TNFRSF10A	O00220	22	T1DM, T2DM, GDM	No	0.00	0.60	0.42	0.76
MAP3K5	Q99683	17	T1DM, T2DM	No	0.64	0.90	0.00	0.96
CAV1	Q03135	16	T1DM, T2DM, GDM, Other	No	0.48	0.00	0.46	0.71
FASLG	P48023	12	T1DM, T2DM, Other	No	0.65	0.90	0.90	1.00
FAF1	Q9UNN5	12	T2DM	No	0.50	0.90	0.45	0.97
TNFRSF10B	O14763	11	T1DM, T2DM	No	0.29	0.60	0.00	0.70
PLCG1	P19174	11	T2DM	No	0.27	0.00	0.61	0.70
RIPK1	Q13546	10	—	No	0.44	0.90	0.47	0.97
CASP10	Q92851	10	—	No	0.52	0.90	0.47	0.97
FAIM2	Q9BWQ8	10	T2DM, GDM	No	0.27	0.90	0.00	0.92
CFLAR	O15519	9	T2DM	No	0.49	0.90	0.45	0.97
SRC	P12931	9	T1DM, T2DM	No	0.48	0.90	0.20	0.95
BTK	Q06187	9	—	No	0.00	0.90	0.07	0.90
SYK	P43405	9	Other	No	0.00	0.90	0.00	0.90
SUMO1	P63165	9	T1DM, T2DM	No	0.48	0.00	0.61	0.79
CASP8	Q14790	8	T1DM, T2DM	No	0.53	0.90	0.94	1.00
FADD	Q13158	8	T1DM	No	0.95	0.90	0.91	1.00
EGFR	P00533	7	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.75	0.75
DAXX	Q9UER7	—	T1DM	No	0.66	0.90	0.39	0.98
TRADD	Q15628	—	—	No	0.46	0.90	0.28	0.96
CALM1	P0DP23	—	T1DM, GDM	No	0.80	0.00	0.00	0.80
GDF15
RET	P07949	5	T1DM, T2DM, Other	No	0.80	0.00	0.27	0.85
GFRAL	Q6UXV0	4	T2DM	No	0.80	0.00	0.90	0.98
IL18R1
IL18	Q14116	19	T1DM, T2DM, GDM, Other	Abbasi et al, 2016	0.93	0.90	0.91	1.00
IL37	Q9NZH6	13	T1DM, T2DM, GDM	No	0.28	0.60	0.78	0.93
IL18RAP	O95256	12	T1DM	No	0.80	0.90	0.91	1.00
SIGIRR	Q6IA17	12	—	No	0.00	0.60	0.60	0.84
RTN4R
ANPEP	P15144	9	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.90	0.90
APP	P05067	9	T1DM, T2DM, GDM, Other	No	0.05	0.00	0.84	0.84
NGFR	P08138	8	T1DM, T2DM	No	0.50	0.90	0.90	0.99
MAG	P20916	8	—	No	0.24	0.90	0.73	0.98
ARHGDIA	P52565	7	T1DM, Other	No	0.00	0.90	0.00	0.90
RTN4	Q9NQC3	6	T2DM	No	0.24	0.90	0.90	0.99
LINGO1	Q96FE5	5	T2DM	No	0.48	0.90	0.90	0.99
OMG	P23515	5	T2DM	No	0.30	0.90	0.90	0.99
TNFRSF19	Q9NS68	3	—	No	0.00	0.00	0.88	0.88
TNF	P01375	—	T1DM, T2DM, GDM, Other	No	0.00	0.00	0.88	0.88

About

Summary table showing all interaction partners for each target together with additional information:

UniProt ID (UniProt): Link to UniProt for additional information on the target
Diabetes textmining % (in-house data): Percentage of co-mentions from textmining relating to diabetes vs. all other diseases. For more information on the data source, see Westergaard et al. PLoS Computational Biology 2018)
Diabetes associations (Open Targets): Gene-disease (diabetes mellitus) association through experiments or clinical trials. Direct associations with T1DM, T2DM and GDM are shown specifically, while all other diabetes mellitus diseases are included in “Other”.
Suggested biomarker: Known and suggested biomarkers from Abbasi et al, 2016, RHAPSODY partners (collected by the RHAPSODY biomarker taskforce) and based on PPI-network analysis of known biomarkers (in-house Analysis).
Experimental score: STRING experimental score derived from experimental data, such as, affinity chromatography. The experimental data is extracted from the databases BIND, DIP, GRID, HPRD, IntAct, MINT, and PID.
Database score: STRING database score derived from curated data of Biocarta, BioCyc, GO, KEGG, and Reactome.
Textmining score: STRING textmining score derived from co-occurrence of gene/protein names in abstracts
Combined score: STRING combined score of interaction confidence. Interactions with a combined score > 0.7 is deemed a high-confidence interaction.

High-confidence interaction partners with a confidence score 265 0.156 are shown in blue, while suggested interaction partners are shown in gray.

em-dash (—) indicates that no information was available for the target.

4.2 Over Representation Analysis

4.2.1 Network features

Han Over-represented terms were found for:

Biological process GO-terms, Cellular component GO-terms, Molecular function GO-terms, KEGG pathways, Reactome pathways, Wikipathways, GLAD4U diseases, GLAD4U drugs

Biological process GO-terms

Biological process GO-term enrichment in PPI networks

Cellular component GO-terms

Cellular component GO-term enrichment in PPI networks

Molecular function GO-terms

Molecular function GO-term enrichment in PPI networks

KEGG pathways

KEGG pathways enrichment in PPI networks

Reactome pathways

Reactome pathways enrichment in PPI networks

Wikipathways

$Wikipathways enrichment in PPI networks$

Wikipathways enrichment in PPI networks

GLAD4U diseases

GLAD4U disease enrichment in PPI networks

GLAD4U drugs

GLAD4U drug enrichment in PPI networks

Table

Shared enrichment terms
Term	Source link	Targets	Enrichment ratio	FDR
Biological process GO-terms
membrane lipid metabolic process	link	ENPP7	63	0.00e+00
interferon-gamma production	link	IL18R1	53	5.08e-04
natural killer cell activation	link	IL18R1	38	0.060
liposaccharide metabolic process	link	ENPP7	36	5.55e-05
NIK/NF-kappaB signaling	link	IL18R1	34	0.007
production of molecular mediator of immune response	link	IL18R1	29	0.001
ammonium ion metabolic process	link	ENPP7	27	1.22e-06
necrotic cell death	link	FAS	25	8.41e-10
adaptive thermogenesis	link	IL18R1	19	0.196
lymphocyte mediated immunity	link	IL18R1	18	0.028
regulation of DNA-binding transcription factor activity	link	IL18R1	17	0.001
lymphocyte activation involved in immune response	link	IL18R1	17	0.215
positive regulation of cytokine production	link	IL18R1	16	0.001
extrinsic apoptotic signaling pathway	link	FAS	15	0.00e+00
adaptive immune response	link	IL18R1	15	0.007
regulation of immune effector process	link	IL18R1	14	0.008
activation of protein kinase activity	link	GDF15	12	4.72e-14
response to transforming growth factor beta	link	GDF15	11	2.11e-08
regulation of apoptotic signaling pathway	link	FAS	10	0.00e+00
positive regulation of proteolysis	link	FAS	10	0.00e+00
lipid catabolic process	link	ENPP7	10	0.061
response to BMP	link	GDF15	10	3.21e-04
regulation of peptidase activity	link	FAS	9	0.00e+00
transmembrane receptor protein serine/threonine kinase signaling pathway	link	GDF15	9	5.61e-08
phospholipid metabolic process	link	ENPP7	8	0.040
regulation of protein serine/threonine kinase activity	link	GDF15	8	8.41e-11
protein kinase B signaling	link	GDF15	8	1.44e-05
feeding behavior	link	GDF15	8	0.048
response to mechanical stimulus	link	FAS	7	3.11e-06
response to peptide	link	GDF15	7	2.76e-09
response to axon injury	link	RTN4R	7	0.009
cellular response to external stimulus	link	FAS	6	1.10e-07
stress-activated protein kinase signaling cascade	link	FAS	6	1.40e-06
T cell activation	link	IL18R1	6	0.630
multicellular organismal homeostasis	link	IL18R1	6	0.640
leukocyte differentiation	link	IL18R1	6	0.678
regulation of developmental growth	link	GDF15	6	8.03e-04
cellular response to environmental stimulus	link	FAS	5	2.62e-05
negative regulation of growth	link	GDF15	5	0.004
negative regulation of cell projection organization	link	RTN4R	5	0.001
regeneration	link	RTN4R	5	0.001
response to nutrient levels	link	FAS	4	1.40e-04
response to oxygen levels	link	FAS	4	0.001
multicellular organism growth	link	GDF15	4	0.150
cell-cell fusion	link	GDF15	4	0.510
syncytium formation	link	GDF15	4	0.516
axon development	link	RTN4R	4	1.74e-08
negative regulation of nervous system development	link	RTN4R	4	3.16e-04
negative regulation of cell development	link	RTN4R	4	0.002
response to nutrient levels	link	GDF15	3	0.063
regulation of neuron projection development	link	RTN4R	3	9.25e-05
regulation of cell morphogenesis	link	RTN4R	3	0.006
developmental growth involved in morphogenesis	link	RTN4R	3	0.023
negative regulation of growth	link	RTN4R	3	0.045
forebrain development	link	RTN4R	3	0.095
muscle cell differentiation	link	GDF15	2	0.269
cell growth	link	RTN4R	2	0.039
regulation of developmental growth	link	RTN4R	2	0.295
negative regulation of response to external stimulus	link	RTN4R	2	0.474
regulation of response to wounding	link	RTN4R	2	0.522
regulation of anatomical structure size	link	RTN4R	1	0.956
Cellular component GO-terms
membrane region	link	FAS	8	1.15e-12
dendritic shaft	link	RTN4R	4	0.669
membrane region	link	RTN4R	3	0.002
glutamatergic synapse	link	RTN4R	3	0.005
anchored component of membrane	link	RTN4R	3	0.254
presynapse	link	RTN4R	2	0.060
neuronal cell body	link	RTN4R	2	0.062
GLAD4U diseases
Parotitis	link	IL18R1	70	0.298
Purpura, Thrombocytopenic	link	IL18R1	53	0.033
Purpura, Thrombocytopenic, Idiopathic	link	IL18R1	49	0.037
Purpura	link	IL18R1	43	0.043
Actinomycetales Infections	link	IL18R1	38	6.83e-04
Mycobacterial infection	link	IL18R1	37	6.83e-04
Mycobacterium Infections	link	IL18R1	37	6.83e-04
Environmental allergy	link	IL18R1	36	0.005
Periventricular leucomalacia	link	FAS	34	0.005
Psoriasis	link	IL18R1	31	0.001
Graves Disease	link	IL18R1	30	0.008
Osteoarthritis, Knee	link	IL18R1	30	0.069
Mumps	link	IL18R1	26	0.492
Osteoarthritis	link	IL18R1	25	0.013
Malabsorption Syndromes	link	IL18R1	24	0.099
Smallpox	link	IL18R1	24	0.099
Gastroenteritis	link	IL18R1	23	6.37e-04
Asthma	link	IL18R1	23	6.37e-04
Crohn Disease	link	IL18R1	23	0.002
Occupational Diseases	link	IL18R1	23	0.100
Respiratory Hypersensitivity	link	IL18R1	22	0.002
Gram-Positive Bacterial Infections	link	IL18R1	22	0.017
Leprosy	link	IL18R1	21	0.572
Hyperoxia	link	FAS	20	4.52e-04
hepatic necrosis	link	FAS	19	8.87e-06
Rubella	link	IL18R1	19	0.601
Inflammatory Bowel Diseases	link	IL18R1	18	0.004
Bronchial Diseases	link	IL18R1	17	0.005
Hypersensitivity	link	IL18R1	17	0.005
Preterm Infant	link	IL18R1	17	0.033
Respiratory Syncytial Virus Infections	link	IL18R1	17	0.033
Celiac Disease	link	IL18R1	17	0.161
Lymphopenia	link	FAS	16	8.00e-07
Lymphocytosis	link	FAS	16	0.006
Bronchitis	link	IL18R1	16	0.038
Inflammation	link	IL18R1	14	6.83e-04
Respiratory Tract Infections	link	IL18R1	14	0.047
Traumatic optic neuropathy	link	RTN4R	14	0.181
Multiple Sclerosis, Relapsing-Remitting	link	FAS	13	6.07e-04
Toxemia	link	FAS	13	0.035
Systemic sclerosis, diffuse	link	GDF15	13	0.056
Drug interaction with food	link	GDF15	13	0.221
Erythema	link	FAS	12	0.013
Vaccinia	link	IL18R1	12	0.782
Hypertension, Pulmonary	link	GDF15	12	3.49e-04
Hypertrophy, Left Ventricular	link	GDF15	12	0.018
Bronchopulmonary dysplasia of newborn	link	GDF15	12	0.069
Death	link	FAS	11	0.00e+00
Thyroiditis	link	FAS	11	0.005
Bronchiolitis	link	IL18R1	11	0.290
Cachexia	link	GDF15	11	0.270
Drug interaction with drug	link	FAS	10	0.00e+00
Hodgkin Disease	link	FAS	10	6.46e-07
Lung Diseases	link	IL18R1	10	0.094
Respiratory Tract Diseases	link	IL18R1	10	0.100
Bacterial Infections	link	IL18R1	10	0.321
Growth Disorders	link	GDF15	10	3.48e-06
Bone Neoplasms	link	GDF15	10	7.77e-05
Lymphoma, B-Cell	link	FAS	9	1.80e-08
Brain Death	link	FAS	9	2.03e-06
Tumor Virus Infections	link	FAS	9	4.36e-06
Lymphoma, T-Cell, Peripheral	link	FAS	9	0.021
Xerostomia	link	FAS	9	0.023
dry mouth	link	FAS	9	0.023
Pathologic Processes	link	IL18R1	9	0.035
Anorexia	link	GDF15	9	0.139
beta-Thalassemia	link	GDF15	9	0.788
Necrosis	link	FAS	8	1.00e-12
Lymphoma, Low-Grade	link	FAS	8	9.41e-08
Leukopenia	link	FAS	8	0.005
Cross Infection	link	FAS	8	0.013
Goiter	link	FAS	8	0.013
Splenomegaly	link	FAS	8	0.088
Sezary Syndrome	link	FAS	8	0.096
Thyroiditis, Autoimmune	link	FAS	8	0.096
overall survival	link	GDF15	8	6.73e-10
major adverse cardiac events (mace)	link	GDF15	8	0.837
Spinal Cord Injuries	link	RTN4R	8	0.325
Lymphoma	link	FAS	7	1.47e-08
Lupus erythematosus	link	FAS	7	3.60e-05
Lupus Erythematosus, Systemic	link	FAS	7	3.60e-05
Lymphoma, Non-Hodgkin	link	FAS	7	1.80e-04
Neoplasms, Radiation-Induced	link	FAS	7	0.001
Neutropenia	link	FAS	7	0.011
Hepatitis C, Chronic	link	FAS	7	0.019
Lung Diseases, Interstitial	link	FAS	7	0.021
Dry Eye Syndromes	link	FAS	7	0.041
Brain Death	link	GDF15	7	0.012
Hyperoxia	link	GDF15	7	0.869
overall survival	link	FAS	6	1.68e-11
Lymphoproliferative Disorders	link	FAS	6	2.10e-07
Lymphatic Diseases	link	FAS	6	4.36e-06
autoimmunity	link	FAS	6	5.46e-04
Leukemia, B-Cell	link	FAS	6	0.003
Lymphoma, T-Cell	link	FAS	6	0.005
Hepatitis, Chronic	link	FAS	6	0.010
Hepatitis B	link	FAS	6	0.011
Lymphoma, T-Cell, Cutaneous	link	FAS	6	0.156
Hepatitis, Autoimmune	link	FAS	6	0.291
Endotoxemia	link	FAS	6	0.310
Autoimmune hemolytic anemia NOS	link	FAS	6	0.635
Intestinal Diseases	link	IL18R1	6	0.489
Colorectal Neoplasms	link	GDF15	6	5.77e-04
Intestinal Neoplasms	link	GDF15	6	6.88e-04
Eating Disorders	link	GDF15	6	0.046
Scleroderma, Systemic	link	GDF15	6	0.229
Hemolysis	link	GDF15	6	0.493
Anemia, Hypochromic	link	GDF15	6	0.952
Embolism	link	GDF15	6	0.952
Leukemia	link	FAS	5	4.41e-07
Acquired Immunodeficiency Syndrome	link	FAS	5	0.020
Occupational Diseases	link	FAS	5	0.128
Cervical Intraepithelial Neoplasia	link	FAS	5	0.407
Death	link	GDF15	5	0.004
Glioblastoma	link	GDF15	5	0.110
Polyps	link	GDF15	5	0.631
Ectopic pregnancy NOS	link	GDF15	5	0.969
Thalassemia	link	GDF15	5	0.969
Anemia, Iron-Deficiency	link	GDF15	5	0.974
Hemochromatosis	link	GDF15	5	0.974
Spinal Cord Diseases	link	RTN4R	5	0.012
Spinal Injuries	link	RTN4R	5	0.832
Autoimmune Diseases	link	FAS	4	0.002
Immunologic Deficiency Syndromes	link	FAS	4	0.002
Connective Tissue Diseases	link	FAS	4	0.003
HIV Infections	link	FAS	4	0.005
Arthritis	link	FAS	4	0.011
Arthritis, Rheumatoid	link	FAS	4	0.013
Leukemia, Lymphoid	link	FAS	4	0.015
Lymphoid leukemia NOS	link	FAS	4	0.015
Leukemia, T-Cell	link	FAS	4	0.023
Multiple Sclerosis	link	FAS	4	0.028
Hepatitis	link	FAS	4	0.044
Uterine Cervical Neoplasms	link	FAS	4	0.088
Rupture	link	FAS	4	0.106
transplant rejection	link	FAS	4	0.154
Sepsis	link	FAS	4	0.199
Septicemia	link	FAS	4	0.204
Autoimmune Thyroid Disease	link	FAS	4	0.251
Pregnancy First Trimester	link	FAS	4	0.360
Gastrointestinal Diseases	link	GDF15	4	0.016
Neoplasm of unspecified nature of digestive system	link	GDF15	4	0.036
Gastrointestinal Neoplasms	link	GDF15	4	0.043
Urogenital Neoplasms	link	GDF15	4	0.068
Hypertension	link	GDF15	4	0.117
Disease Progression	link	GDF15	4	0.139
Recurrence	link	GDF15	4	0.296
Hypertrophy	link	GDF15	4	0.497
Hemostatic Disorders	link	GDF15	4	0.550
Pulmonary Heart Disease	link	GDF15	4	0.665
Body Weight Changes	link	GDF15	4	0.671
Multiple Sclerosis	link	RTN4R	4	0.139
Retroviridae Infections	link	FAS	3	0.011
Sexually Transmitted Diseases	link	FAS	3	0.011
Skin and Connective Tissue Diseases	link	FAS	3	0.011
Lentivirus Infections	link	FAS	3	0.011
Rheumatic Diseases	link	FAS	3	0.044
Joint Diseases	link	FAS	3	0.083
Obstetric Labor Complications	link	FAS	3	0.107
Premature Birth	link	FAS	3	0.201
Demyelinating Diseases	link	FAS	3	0.203
Gestational hypertension	link	FAS	3	0.246
Hepatitis C	link	FAS	3	0.370
Disorder of uterus NOS	link	FAS	3	0.401
Uterine Neoplasms	link	FAS	3	0.401
Organ Transplantation	link	FAS	3	0.502
Pre-Eclampsia	link	FAS	3	0.505
Eclampsia	link	FAS	3	0.510
Mycosis Fungoides	link	FAS	3	0.832
Inflammation	link	GDF15	3	0.296
Pregnancy	link	GDF15	3	0.667
Ischemia	link	GDF15	3	0.718
Renal diabetes	link	GDF15	3	0.888
Pregnancy Complications	link	FAS	2	0.656
Male Urogenital Diseases	link	GDF15	2	0.579
Hematologic Diseases	link	GDF15	2	0.767
Nutrition Disorders	link	GDF15	2	0.934
Vascular Diseases	link	GDF15	2	0.954
Central Nervous System Diseases	link	RTN4R	2	0.792
GLAD4U drugs
Allergen extracts	link	IL18R1	77	0.946
nystatin	link	FAS	33	1.63e-06
Interleukins	link	IL18R1	27	5.25e-08
interferons	link	IL18R1	25	1.19e-06
Viral Vaccines	link	IL18R1	19	0.543
antithymocyte globulin	link	FAS	18	0.075
apixaban	link	GDF15	18	0.961
antivirals	link	IL18R1	17	1.90e-04
trifluoperazine	link	FAS	16	0.003
Immunostimulants	link	IL18R1	16	0.122
Tumor necrosis factor alpha (TNF-alpha) inhibitors	link	FAS	15	0.00e+00
Antiinfectives	link	IL18R1	15	3.34e-04
Vaccines	link	IL18R1	15	0.733
Antiseptics And Disinfectants	link	FAS	13	0.028
epipodophyllotoxin	link	FAS	12	7.22e-08
podofilox	link	FAS	12	7.22e-08
Bone morphogenetic proteins	link	GDF15	12	5.26e-06
etoposide	link	FAS	11	4.83e-08
phospholipids	link	ENPP7	11	1.23e-04
ginseng	link	RTN4R	11	0.469
doxorubicin	link	FAS	8	5.72e-05
Drugs For Functional Gastrointestinal Disorders	link	GDF15	8	0.216
Proteinase inhibitors	link	FAS	7	2.46e-10
highly active antiretroviral therapy (haart)	link	FAS	7	0.011
Immunoglobulins	link	IL18R1	7	0.731
immune globulin	link	IL18R1	7	0.731
protease inhibitors	link	FAS	6	1.88e-07
Alkylating Agents	link	FAS	6	0.001
docetaxel	link	GDF15	6	0.834
Immunoglobulins	link	FAS	5	6.33e-07
immune globulin	link	FAS	5	6.33e-07
Antiinfectives	link	FAS	5	2.00e-06
antivirals	link	FAS	5	3.80e-05
Monoclonal antibodies	link	FAS	4	7.18e-04
interferons	link	FAS	4	0.005
Immunosuppressants	link	FAS	4	0.010
biotin	link	FAS	4	0.057
oxaliplatin	link	FAS	4	0.634
trichostatin A	link	GDF15	4	0.891
Tumour Detection	link	GDF15	3	0.977
l-leucine	link	RTN4R	2	0.370
KEGG pathways
Sphingolipid metabolism	link	ENPP7	136	0.00e+00
Inflammatory bowel disease (IBD)	link	IL18R1	40	0.007
Cytokine-cytokine receptor interaction	link	IL18R1	15	0.002
Apoptosis	link	FAS	12	0.00e+00
TNF signaling pathway	link	FAS	11	1.49e-11
Natural killer cell mediated cytotoxicity	link	FAS	10	4.69e-10
Necroptosis	link	FAS	9	4.90e-11
Chagas disease (American trypanosomiasis)	link	FAS	9	2.54e-07
Platinum drug resistance	link	FAS	9	9.39e-06
African trypanosomiasis	link	FAS	9	0.006
Kaposi sarcoma-associated herpesvirus infection	link	FAS	8	4.90e-11
Allograft rejection	link	FAS	8	0.007
Human cytomegalovirus infection	link	FAS	7	1.90e-10
Epstein-Barr virus infection	link	FAS	7	2.77e-10
Human immunodeficiency virus 1 infection	link	FAS	7	3.67e-09
Hepatitis B	link	FAS	7	6.57e-07
Measles	link	FAS	7	1.35e-06
Type I diabetes mellitus	link	FAS	7	0.012
Proteoglycans in cancer	link	FAS	6	1.47e-08
Herpes simplex infection	link	FAS	6	2.54e-07
Influenza A	link	FAS	6	6.92e-07
Non-alcoholic fatty liver disease (NAFLD)	link	FAS	6	9.39e-06
p53 signaling pathway	link	FAS	6	0.003
Graft-versus-host disease	link	FAS	6	0.046
Alzheimer disease	link	FAS	5	1.36e-04
Autoimmune thyroid disease	link	FAS	5	0.063
MAPK signaling pathway	link	FAS	4	3.11e-04
Cytokine-cytokine receptor interaction	link	GDF15	4	0.019
Pathways in cancer	link	FAS	3	1.13e-04
Human papillomavirus infection	link	FAS	3	0.002
Cytokine-cytokine receptor interaction	link	FAS	3	0.005
Molecular function GO-terms
cytokine receptor activity	link	IL18R1	29	0.274
cytokine binding	link	IL18R1	21	0.361
phosphoric ester hydrolase activity	link	ENPP7	10	0.032
sphingolipid binding	link	RTN4R	9	0.328
glycolipid binding	link	RTN4R	9	0.328
cytokine receptor binding	link	GDF15	4	0.076
glycosaminoglycan binding	link	RTN4R	3	0.214
sulfur compound binding	link	RTN4R	3	0.318
Reactome pathways
Interleukin-37 signaling	link	IL18R1	124	6.56e-04
Sphingolipid metabolism	link	ENPP7	103	0.00e+00
CASP8 activity is inhibited	link	FAS	94	0.00e+00
Regulation by c-FLIP	link	FAS	94	0.00e+00
Dimerization of procaspase-8	link	FAS	94	0.00e+00
Caspase activation via Death Receptors in the presence of ligand	link	FAS	65	0.00e+00
Glycosphingolipid metabolism	link	ENPP7	64	4.30e-06
Regulation of necroptotic cell death	link	FAS	57	0.00e+00
RIPK1-mediated regulated necrosis	link	FAS	52	0.00e+00
Regulated Necrosis	link	FAS	52	0.00e+00
Interleukin-1 family signaling	link	IL18R1	50	3.34e-10
Caspase activation via extrinsic apoptotic signalling pathway	link	FAS	47	0.00e+00
TP53 Regulates Transcription of Death Receptors and Ligands	link	FAS	31	1.87e-04
TP53 Regulates Transcription of Cell Death Genes	link	FAS	15	1.45e-05
Signaling by Interleukins	link	IL18R1	15	2.60e-06
Death Receptor Signalling	link	FAS	13	3.29e-14
Apoptosis	link	FAS	10	1.02e-11
Programmed Cell Death	link	FAS	10	1.27e-11
p75 NTR receptor-mediated signalling	link	RTN4R	4	0.066
Transcriptional Regulation by TP53	link	FAS	3	0.020
Death Receptor Signalling	link	RTN4R	3	0.094
Wikipathways
Apoptosis Modulation by HSP70	link	FAS	33	1.42e-10
Nanomaterial induced apoptosis	link	FAS	28	7.34e-09
Selective expression of chemokine receptors during T-cell polarization	link	IL18R1	27	0.926
Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation	link	FAS	20	3.57e-11
Apoptosis Modulation and Signaling	link	FAS	17	0.00e+00
Apoptosis	link	FAS	17	0.00e+00
Photodynamic therapy-induced AP-1 survival signaling.	link	FAS	16	3.46e-09
IL-18 signaling pathway	link	IL18R1	15	2.21e-04
Alzheimers Disease	link	FAS	10	2.50e-07
Hepatitis B infection	link	FAS	8	3.25e-08
Spinal Cord Injury	link	RTN4R	8	5.00e-07
Allograft Rejection	link	FAS	7	3.03e-04
DNA Damage Response	link	FAS	7	4.27e-04
miRNA Regulation of DNA Damage Response	link	FAS	7	4.94e-04
Nonalcoholic fatty liver disease	link	FAS	6	2.06e-05
T-Cell antigen Receptor (TCR) Signaling Pathway	link	FAS	6	0.002
Control of immune tolerance by vasoactive intestinal peptide	link	FAS	6	0.425
IL-18 signaling pathway	link	FAS	4	2.12e-04
MAPK Signaling Pathway	link	FAS	4	2.45e-04
VEGFA-VEGFR2 Signaling Pathway	link	FAS	3	0.002
Adipogenesis	link	FAS	3	0.111
Genes involved in male infertility	link	FAS	2	0.526
Epithelial to mesenchymal transition in colorectal cancer	link	GDF15	2	0.700
22q11.2 Deletion Syndrome	link	RTN4R	2	0.939
Circadian rhythm related genes	link	FAS	1	0.896

About

Over-representation analysis (ORA) conducted using WebGestaltR (see tool-publication here). Enriched terms are calculated based on the supplied targets as a collected group against all transcripts/proteins measured in RHAPSODY.
Significant terms with a FDR-adjusted p-value < 0.05 are shown in blue, while non-significant terms are shown in gray. The genes/proteins affiliated with the term are shown to the right of the barplot.

Unfortunately, the analysis will not always have an output. In these cases the following error message will be shown: Unfortunately, no enriched GO-terms were found for the selected targets.

4.2.2 Shared features

Over-represented terms were found for:

KEGG pathways, GLAD4U diseases, GLAD4U drugs

Biological process GO-terms

## [1] "Unfortunately, no enriched terms were found for the selected targets."

Cellular component GO-terms

## [1] "Unfortunately, no enriched terms were found for the selected targets."

Molecular function GO-terms

## [1] "Unfortunately, no enriched terms were found for the selected targets."

KEGG pathways

Shared KEGG pathway enrichment

Reactome pathways

## [1] "Unfortunately, no enriched terms were found for the selected targets."

Wikipathways

## [1] "Unfortunately, no enriched terms were found for the selected targets."

GLAD4U diseases

Shared GLAD4U disease enrichment

GLAD4U drugs

Shared GLAD4U drug enrichment

Table

Shared enrichment terms
Term	Source link	Targets	Enrichment ratio	FDR
GLAD4U diseases
Periventricular leucomalacia	link	FAS	205	0.880
Endocardial Cushion Defects	link	CRELD1	186	0.880
Hyperoxia	link	FAS, GDF15	146	0.169
Parotitis	link	IL18R1	128	0.880
Traumatic optic neuropathy	link	RTN4R	120	0.880
Autoimmune hemolytic anemia NOS	link	FAS	102	0.880
beta-Thalassemia	link	GDF15	97	0.880
Mitral Valve Insufficiency	link	CRELD1	97	0.880
major adverse cardiac events (mace)	link	GDF15	85	0.880
Cholelithiasis	link	ENPP7	82	0.880
Cholangitis, Sclerosing	link	ENPP7	76	0.880
Toxemia	link	FAS	76	0.880
Spinal Cord Injuries	link	RTN4R	73	0.880
Drug interaction with food	link	GDF15	71	0.880
Lymphocytosis	link	FAS	71	0.880
Heart Septal Defects, Ventricular	link	CRELD1	64	0.880
Anemia, Hypochromic	link	GDF15	62	0.880
Embolism	link	GDF15	62	0.880
Heart Septal Defects, Atrial	link	CRELD1	62	0.880
Cachexia	link	GDF15	60	0.880
Hypoparathyroidism	link	RTN4R	60	0.880
Spinal Injuries	link	RTN4R	60	0.880
Hepatitis, Autoimmune	link	FAS	58	0.880
Ostium secundum type atrial septal defect	link	CRELD1	58	0.880
Ectopic pregnancy NOS	link	GDF15	57	0.880
Thalassemia	link	GDF15	57	0.880
Anemia, Iron-Deficiency	link	GDF15	55	0.880
Endotoxemia	link	FAS	55	0.880
Hemochromatosis	link	GDF15	55	0.880
Mycosis Fungoides	link	FAS	54	0.880
DiGeorge Syndrome	link	RTN4R	52	0.880
Erythema	link	FAS	52	0.880
hepatic necrosis	link	FAS	50	0.880
Systemic sclerosis, diffuse	link	GDF15	50	0.880
Purpura, Thrombocytopenic	link	IL18R1	49	0.880
Splenomegaly	link	FAS	49	0.880
Mumps	link	IL18R1	48	0.880
Septal defect NOS	link	CRELD1	47	0.880
Sezary Syndrome	link	FAS	47	0.880
Thyroiditis, Autoimmune	link	FAS	47	0.880
Bronchopulmonary dysplasia of newborn	link	GDF15	45	0.880
Hemoglobinopathies	link	GDF15	45	0.880
Cervical Intraepithelial Neoplasia	link	FAS	44	0.880
Purpura, Thrombocytopenic, Idiopathic	link	IL18R1	44	0.880
adverse cardiovascular events	link	GDF15	43	0.880
Iron Overload	link	GDF15	43	0.880
Lymphoma, T-Cell, Peripheral	link	FAS	43	0.880
Occupational Diseases	link	FAS, IL18R1	43	0.880
dry mouth	link	FAS	41	0.880
Xerostomia	link	FAS	41	0.880
gastrointestinal toxicity	link	GDF15	39	0.880
Leprosy	link	IL18R1	39	0.880
Multiple Sclerosis, Relapsing-Remitting	link	FAS	39	0.880
Purpura	link	IL18R1	39	0.880
Relapsing pancreatitis	link	GDF15	39	0.880
Thyroiditis	link	FAS	39	0.880
Angina, Unstable	link	GDF15	37	0.880
Cholangitis	link	ENPP7	37	0.880
Congenital haemolytic anaemia	link	GDF15	36	0.880
Hereditary hemolytic anemia NOS	link	GDF15	36	0.880
Lymphoma, T-Cell, Cutaneous	link	FAS	36	0.880
Hemolysis	link	GDF15	35	0.880
Rubella	link	IL18R1	35	0.880
Dry Eye Syndromes	link	FAS	34	0.895
Hypertrophy, Left Ventricular	link	GDF15	34	0.895
Anorexia	link	GDF15	32	0.895
Brain Infarction	link	GDF15	32	0.895
Lymphopenia	link	FAS	32	0.895
Peripheral Vascular Diseases	link	GDF15	32	0.895
Angina Pectoris	link	GDF15	31	0.925
Cross Infection	link	FAS	29	0.942
Goiter	link	FAS	29	0.942
Acute coronary syndrome	link	GDF15	28	0.957
Osteoarthritis, Knee	link	IL18R1	28	0.971
adverse events	link	GDF15	27	0.972
Autoimmune Thyroid Disease	link	FAS	27	0.973
Polyps	link	GDF15	27	0.975
Brain Death	link	FAS, GDF15	26	0.880
Anemia, Hemolytic	link	GDF15	25	0.981
Atrial Fibrillation	link	GDF15	25	0.981
Body Weight Changes	link	GDF15	25	0.981
Hepatitis C, Chronic	link	FAS	25	0.981
Leukopenia	link	FAS	25	0.981
Pulmonary Heart Disease	link	GDF15	25	0.981
Lung Diseases, Interstitial	link	FAS	24	0.982
Scleroderma, Systemic	link	GDF15	24	0.984
Trisomy	link	CRELD1	24	0.983
Multiple Sclerosis	link	FAS, RTN4R	22	0.880
Growth Disorders	link	GDF15, RTN4R	21	0.880
Intestinal Diseases	link	IL18R1, ENPP7	12	0.880
Death	link	FAS, GDF15	11	0.880
Heart Diseases	link	CRELD1, GDF15	10	0.880
Cardiovascular Diseases	link	CRELD1, GDF15	9	0.880
overall survival	link	FAS, GDF15	9	0.880
Inflammation	link	IL18R1, GDF15	8	0.880
GLAD4U drugs
Antiinfectives	link	FAS, IL18R1, GDF15	16	0.637
KEGG pathways
TNF signaling pathway	link	FAS, IL18R1	29	0.279
Cytokine-cytokine receptor interaction	link	FAS, IL18R1, GDF15	18	0.083

About

Over-represtation analysis (ORA) conducted using WebGestaltR (see tool-publication here). Enriched terms are calculated based on the supplied targets as a collected group against all transcripts/proteins measured in RHAPSODY.
Significant terms with a FDR-adjusted p-value < 0.05 are shown in blue, while non-significant terms are shown in gray. The genes/proteins affiliated with the term are shown to the right of the barplot.

Unfortunately, the analysis will not always have an output. In these cases the following error message will be shown: Unfortunately, no enriched GO-terms were found for the selected targets.

5 Biomarker potential

5.1 Drug interactions

Table

Drug interactions
	ATC codes	Drug groups	Target type	Pharmacological action	Evidence for interaction
CRELD1
—	—	—	—	—	—
ENPP7
—	—	—	—	—	—
FAS
—	—	—	—	—	—
GDF15
—	—	—	—	—	—
IL18R1
—	—	—	—	—	—
RTN4R
—	—	—	—	—	—

About

Table of target-drug interactions from DrugBank:

ATC codes: Associated ATC code(s). For further information on the ATC system, see the WHO Collaborating Centre for Drug Statistics’ website.
Drug groups: Drugs are categorized by group determined by their drug development status.:
- Approved: A drug that has been approved in at least one jurisdiction, at some point in time. This does not mean the drug is currently approved or available, just that it has been approved and marketed at some point, somewhere. Different jurisdictions also have a different concept for “approval”. For example drugs that are available over-the-counter in the U.S. may not be technically approved, whereas over-the-counter drugs in Canada are considered approved.
- Vet Approved: A drug that has been approved in at least one jurisdiction, at some point in time for the treatment of animals.
- Nutraceutical: A drug that is a pharmaceutical-grade and standardized nutrient (with confirmed or unconfirmed health benefits).
- Illicit: A drug that is scheduled in at least one jurisdiction, at some point in time.
- Withdrawn: A previously approved drug that has been withdrawn from the market in at least one jurisdiction, at some point in time. Note that because a drug can be approved in one jurisdiction, and withdrawn in another, it’s possible for a drug to be in both groups. If a drug has been approved at some point in time, and then withdrawn, it would also be in both drug groups.
- Investigational: A drug that is in some phase of the drug approval process in at least one jurisdiction.
- Experimental: A compound that has been shown experimentally to bind specific proteins in mammals, bacteria, viruses, fungi, or parasites. This includes compounds that are Pre-Investigational New Drug Applications (Pre-IND, or Discovery Phase compounds).
Target type: Protein targets of drug action, enzymes that are inhibited/induced or involved in metabolism, and carrier or transporter proteins involved in movement of the drug across biological membranes. Colored according to type using color scheme from DrugBank.
Pharmacological action:
- Yes: A interaction is marked as ‘Yes’ if the drug interacts directly with the target as part of the drug’s mechanism of action.
- No: A interaction is marked as ‘No’ if the interaction between target and drug is not directly involved in the drug’s mechanism of action.
- Unknown: A interaction is marked as ‘Unknown’ if currently there is no formal research or evidence to elucidate whether interaction between the target and drug is associated with the drug’s mechanism of action at all. Colored according to action using color scheme from DrugBank.
Evidence for interaction: Link to the target-drug interaction information on the DrugBank website with references to primary literature on the interaction.

5.2 Antibody count

Plot

Antibody availability

About

Antibody count from PHAROS (data originates from antibodypedia).

Total antibody count: Total number of commercially available antibodies of any type.
Monoclonal antibodies: Number of commercially available monoclonal antibodies.
Polyclonal antibodies: Derived number of commercially available polyclonal antibodies. Calculated from total and monoclonal antibodies. This should only be considered an estimate, as a small minority of antibodies fall outside of the two categories of monoclonal and polyclonal antibodies, e.g. recombinant antibodies.

5.3 Novelty

Plot

Novelty

About

The novelty scores shown here is pulled from PHAROS. This score is calculated from text mining results using the formula $N_{i} = \frac{1}{\sum \frac{1}{T_{k}}}$, where $N_{i}$ is the novelty score for the target $i$ and $T_{k}$ is the number of targets in abstracts $k$. The $\log_{10}$ value of $N_{i}$ is reported to avoid too high skewness in the data. A more negative value should be interpreted as lower novelty, i.e. the target has been studied/reported more and the target is less novel.

About the report

This report is intended to provide objective measures that can be used to perform informed biomarker prioritization.
It incorporates experimental RHAPSODY data, public data from multiple databases, data from incorporated R-libraries, and in-house generated text-mining data.

Data source overview

RHAPSODY data

Selected targets chosen through the RHAPSODY Biomarker Prioritization interface.
Reference experimental data from all RHAPSODY experiments.

Public data

UniProt website
The Human Protein Atlas (HPA) website
Open Targets website
PHAROS website
DrugBank website
STRING website
WebGestalt website

In-house generated data

Text-mining of 15 million full-text scientific articles Westergaard et al. PLoS Computational Biology 2018

Technical information

Database version information
Database	Version	Version release date	Download date
DrugBank	5.1.9	2022-01-04	2022-07-18
HPA	21.1	2022-05-31	2022-08-04
Open Targets	22.06	2022-06-24	2022-08-04
PHAROS	TCRD v6.12.4	2021-10-29	2022-01-28
UniProt	2022_03	2022-08-03	2022-08-04

## R version 4.2.1 (2022-06-23)
## Platform: x86_64-apple-darwin17.0 (64-bit)
## Running under: macOS Big Sur ... 10.16
## 
## Matrix products: default
## BLAS:   /Library/Frameworks/R.framework/Versions/4.2/Resources/lib/libRblas.0.dylib
## LAPACK: /Library/Frameworks/R.framework/Versions/4.2/Resources/lib/libRlapack.dylib
## 
## locale:
## [1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8
## 
## attached base packages:
## [1] stats     graphics  grDevices utils     datasets  methods   base     
## 
## other attached packages:
##  [1] WebGestaltR_0.4.4  EnvStats_2.7.0     tidygraph_1.2.1    ggraph_2.0.5      
##  [5] Cairo_1.6-0        patchwork_1.1.1    ggnewscale_0.4.7   RColorBrewer_1.1-3
##  [9] ggrepel_0.9.1      formattable_0.2.1  kableExtra_1.3.4   writexl_1.4.0     
## [13] readxl_1.4.0       knitr_1.39         janitor_2.1.0      forcats_0.5.1     
## [17] stringr_1.4.0      dplyr_1.0.9        purrr_0.3.4        readr_2.1.2       
## [21] tidyr_1.2.0        tibble_3.1.7       ggplot2_3.3.6      tidyverse_1.3.1   
## 
## loaded via a namespace (and not attached):
##  [1] colorspace_2.0-3   ellipsis_0.3.2     rprojroot_2.0.3    snakecase_0.11.0  
##  [5] fs_1.5.2           rstudioapi_0.13    farver_2.1.1       graphlayouts_0.8.0
##  [9] bit64_4.0.5        fansi_1.0.3        lubridate_1.8.0    xml2_1.3.3        
## [13] codetools_0.2-18   doParallel_1.0.17  polyclip_1.10-0    jsonlite_1.8.0    
## [17] apcluster_1.4.10   broom_1.0.0        dbplyr_2.2.1       ggforce_0.3.3     
## [21] compiler_4.2.1     httr_1.4.3         backports_1.4.1    assertthat_0.2.1  
## [25] Matrix_1.4-1       fastmap_1.1.0      cli_3.3.0          tweenr_1.0.2      
## [29] htmltools_0.5.2    tools_4.2.1        igraph_1.3.2       gtable_0.3.0      
## [33] glue_1.6.2         doRNG_1.8.2        Rcpp_1.0.9         cellranger_1.1.0  
## [37] jquerylib_0.1.4    vctrs_0.4.1        svglite_2.1.0      iterators_1.0.14  
## [41] xfun_0.31          ps_1.7.1           rvest_1.0.2        lifecycle_1.0.1   
## [45] rngtools_1.5.2     MASS_7.3-57        scales_1.2.0       vroom_1.5.7       
## [49] hms_1.1.1          parallel_4.2.1     curl_4.3.2         yaml_2.3.5        
## [53] gridExtra_2.3      sass_0.4.1         stringi_1.7.8      highr_0.9         
## [57] foreach_1.5.2      rlang_1.0.4        pkgconfig_2.0.3    systemfonts_1.0.4 
## [61] evaluate_0.15      lattice_0.20-45    htmlwidgets_1.5.4  labeling_0.4.2    
## [65] bit_4.0.4          tidyselect_1.1.2   processx_3.7.0     here_1.0.1        
## [69] plyr_1.8.7         magrittr_2.0.3     R6_2.5.1           generics_0.1.3    
## [73] DBI_1.1.3          pillar_1.7.0       haven_2.5.0        whisker_0.4       
## [77] withr_2.5.0        modelr_0.1.8       crayon_1.5.1       utf8_1.2.2        
## [81] tzdb_0.3.0         rmarkdown_2.14     viridis_0.6.2      grid_4.2.1        
## [85] callr_3.7.1        reprex_2.0.1       digest_0.6.29      webshot_0.5.3     
## [89] munsell_0.5.0      viridisLite_0.4.0  bslib_0.3.1

BALDR: Biomarker AnaLysis for Diabetes Research

Version 0.7

Identified targets

1 Functional information

1.1 Target overview

Table

About

1.2 Functionality descriptions

Table

About

2 Experimental evidence

2.1 Volcano plots exploring p-value and effect size relationships

2.1.1 All experimental results for each hit

Plot

About

2.1.2 Compare best experimental result for each target based on p-value

Plot

Table

About

2.2 RHAPSODY meta rank

Table

About

2.3 Best results within tissue and model

Compare across targets

Compare across species

Rank list table

About

Compare across targets

Compare across species

Rank list table

3 Disease association

3.1 Text mining results from public and in-house sources

3.1.1 Disease association in scientific articles

Plot

About

3.1.2 Diabetes fraction of co-mentions

Plot

About

3.2 Open Targets association scores

Diabetes mellitus (EFO_000400)

T2DM (MONDO_0005148)

T1DM (MONDO_0005147)

GDM (EFO_0004593)

Other diabetes mellitus subtypes

About

4 Mechanistic evidence

4.1 Protein-protein interaction network

4.1.1 Network plots

All interactions

High-confidence interactions only

Summary table

About

4.1.2 Interaction partners

All interactions

High-confidence interactions only

About

4.2 Over Representation Analysis

4.2.1 Network features

Biological process GO-terms

Cellular component GO-terms

Molecular function GO-terms

KEGG pathways

Reactome pathways

Wikipathways

GLAD4U diseases

GLAD4U drugs

Table

About

4.2.2 Shared features

Biological process GO-terms

Cellular component GO-terms

Molecular function GO-terms

KEGG pathways

Reactome pathways

Wikipathways

GLAD4U diseases

GLAD4U drugs

Table

About

5 Biomarker potential