CFDE Gene-Centric Appyter: ASXL1

Given the gene ASXL1, we request information about it from several different DCCs in hopes of creating a comprehensive knowledge report for it.

MyGeneInfo: Query

https://mygene.info/

To interoperate with different APIs which support different gene identifier schemes. We'll first use mygene.info to resolve gene identifiers.

{
    "took": 15,
    "total": 743,
    "max_score": 88.29193,
    "hits": [10 items]
}

GeneID: 171023

MyGeneInfo

https://mygene.info/

With the Entrez Gene ID, we can resolve lots of different identifiers and identifiability information from mygene.info.

{
    "AllianceGenome": "18318",
    "HGNC": "18318",
    "MIM": "612990",
    "_id": "171023",
    "_version": 5,
    "accession": {4 items},
    "alias": [2 items],
    "clingen": {2 items},
    "ensembl": {5 items},
    "entrezgene": "171023",
    "exac": {9 items},
    "exons": [3 items],
    "exons_hg19": [3 items],
    "generif": [186 items],
    "genomic_pos": {5 items},
    "genomic_pos_hg19": {4 items},
    "go": {3 items},
    "homologene": {2 items},
    "interpro": [5 items],
    "ipi": [5 items],
    "map_location": "20q11.21",
    "name": "ASXL transcriptional regulator 1",
    "other_names": [4 items],
    "pantherdb": {4 items},
    "pathway": {1 item},
    "pdb": [2 items],
    "pfam": [3 items],
    "pharmgkb": "PA25078",
    "pharos": {1 item},
    "pir": [2 items],
    "prosite": [2 items],
    "reagent": {4 items},
    "refseq": {4 items},
    "reporter": {6 items},
    "retired": 23393,
    "summary": "This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009].",
    "symbol": "ASXL1",
    "taxid": 9606,
    "type_of_gene": "protein-coding",
    "umls": {1 item},
    "unigene": "Hs.374043",
    "uniprot": {2 items},
    "wikipedia": {1 item}
}

Gene Symbol: ASXL1


Primary Information

We query DCC APIs to gain insights about the primary information they collect.

GTEx

https://gtexportal.org/home/

We query the GTEx Data through the GTEx API to identify tissue sites that significantly express the gene question.

Gene with identifier ASXL1 currently not available in GTEx
Could not process GTEx output

LINCS

https://lincsproject.org/

L1000 RNAseq Gene Centric Signature Reverse Search (RGCSRS)

An appyter was built for performing Gene Centric signature reverse searches against the LINCS data. Its functionality is repeated here.

BokehJS 2.4.2 successfully loaded.
Top CRISPR KO signatures where ASXL1 is up-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
XPR008_A549.311_96H_K12_TP53 0.0183 1.0655 0.091484 4919.0 TP53 A549.311 96h
XPR034_MCF7.311_96H_H21_HSD17B10 0.0174 1.0524 0.073726 5097.0 HSD17B10 MCF7.311 96h
XPR036_PC3.311B_96H_G07_UCK1 0.0173 1.0514 0.072274 5349.0 UCK1 PC3.311B 96h
XPR032_A375.311_96H_K19_ALDH1B1 0.0206 1.0511 0.071846 4516.0 ALDH1B1 A375.311 96h
XPR030_HT29.311_96H_M08_S100A12 0.0174 1.0495 0.069706 3930.0 S100A12 HT29.311 96h
XPR017_MCF7.311_96H_G01_GPNMB 0.0183 1.0444 0.062634 5562.0 GPNMB MCF7.311 96h
XPR014_ES2.311_96H_D17_CEP89 0.0194 1.0443 0.062546 4828.0 CEP89 ES2.311 96h
XPR030_A549.311_96H_K12_GSTP1 0.0183 1.0424 0.059972 3735.0 GSTP1 A549.311 96h
XPR032_BICR6.311_96H_F24_GRIN2D 0.0196 1.0409 0.057796 2721.0 GRIN2D BICR6.311 96h
XPR025_MCF7.311_96H_K12_STX11 0.0176 1.0380 0.053769 4499.0 STX11 MCF7.311 96h
Top CRISPR KO signatures where ASXL1 is down-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
XPR043_KYSE30.311_96H_N21_HSPA5 -0.0173 0.9228 -0.115914 4049.0 HSPA5 KYSE30.311 96h
XPR012_BICR6.311_96H_D19_BOC -0.0179 0.9399 -0.089350 3163.0 BOC BICR6.311 96h
XPR018_MCF7.311_96H_J01_IMP4 -0.0183 0.9432 -0.084333 4657.0 IMP4 MCF7.311 96h
XPR020_MCF7.311_96H_N02_MSTO1 -0.0199 0.9446 -0.082226 4042.0 MSTO1 MCF7.311 96h
XPR011_MCF7.311_96H_A03_COASY -0.0179 0.9463 -0.079658 3239.0 COASY MCF7.311 96h
XPR036_A549.311_96H_B18_SH3BP4 -0.0178 0.9516 -0.071547 4812.0 SH3BP4 A549.311 96h
XPR036_ES2.311_96H_N16_LRGUK -0.0195 0.9569 -0.063575 4574.0 LRGUK ES2.311 96h
XPR016_A549.311_96H_C15_DTL -0.0174 0.9601 -0.058691 7064.0 DTL A549.311 96h
XPR019_A549.311_96H_M09_KDM4E -0.0178 0.9602 -0.058553 5446.0 KDM4E A549.311 96h
XPR011_BICR6.311_96H_K24_ACTL6A -0.0174 0.9606 -0.058022 6541.0 ACTL6A BICR6.311 96h
Top Chemical Perturbation signatures where ASXL1 is up-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
REP.A021_MCF7_24H_B19_erteberel_10uM -0.0196 1.3147 0.394762 13303.0 erteberel 10uM MCF7 24h
ERG021_VCAP_24H_P13_WAY-170523_10uM 0.0188 1.2577 0.330840 6208.0 WAY-170523 10uM VCAP 24h
PBIOA017_HA1E_24H_K11_MG-132_10uM 0.0187 1.2144 0.280186 6671.0 MG-132 10uM HA1E 24h
REP.B017_MCF7_24H_O06_MG-132_20uM 0.0210 1.1373 0.185662 5407.0 MG-132 20uM MCF7 24h
LJP005_HEPG2_24H_K21_GDC-0980_1.11uM 0.0203 1.1157 0.157950 4841.0 GDC-0980 1.11uM HEPG2 24h
REP.A012_MDAMB231_24H_L16_celecoxib_0.37uM 0.0201 1.0879 0.121567 3550.0 celecoxib 0.37uM MDAMB231 24h
LJP006_PC3_24H_L09_WYE-125132_1.11uM 0.0190 1.0830 0.114970 4521.0 WYE-125132 1.11uM PC3 24h
CPC010_MCF7_6H_B21_homoveratrylamine_10uM 0.0195 1.0785 0.108974 5426.0 homoveratrylamine 10uM MCF7 6h
ISO002_MCF10A.BRCA1.HD_24H_B11_tofacitinib_0.125uM 0.0224 1.0779 0.108248 6495.0 tofacitinib 0.125uM MCF10A.BRCA1.HD 24h
LJP006_HA1E_24H_L12_WYE-125132_0.04uM 0.0188 1.0740 0.102990 3652.0 WYE-125132 0.04uM HA1E 24h
Top Chemical Perturbation signatures where ASXL1 is down-regulated (based on fold change)
CD Coefficient Fold Change Log2(Fold Change) Rank in Signature Perturbagen Dose Cell Line Timepoint
Signature
LJP005_PC3_24H_C19_mitoxantrone_10uM -0.0203 0.7538 -0.407705 2720.0 mitoxantrone 10uM PC3 24h
CPC006_EFO27_6H_P09_CD-437_12uM -0.0218 0.8490 -0.236205 3264.0 CD-437 12uM EFO27 6h
EMU001_BJAB_6H_F07_doxorubicin_10uM -0.0199 0.8849 -0.176352 5649.0 doxorubicin 10uM BJAB 6h
MUC.CP006_MCF7_24H_N06_SA-1921783_0.37uM -0.0201 0.8858 -0.174936 3749.0 SA-1921783 0.37uM MCF7 24h
CRCGN016_MCF10A.TP53.M_24H_O11_estrone_30uM -0.0217 0.8889 -0.169966 4905.0 estrone 30uM MCF10A.TP53.M 24h
CPC010_A549_24H_J04_VU-0402605_10uM -0.0196 0.8996 -0.152613 6815.0 VU-0402605 10uM A549 24h
HOG002_MCF7_6H_D20_mitoxantrone_0.01uM -0.0270 0.9118 -0.133212 4904.0 mitoxantrone 0.01uM MCF7 6h
MUC.CP004_MCF7_6H_D21_pravastatin_1.11uM -0.0191 0.9127 -0.131779 3929.0 pravastatin 1.11uM MCF7 6h
DOSVAL004_PC3_24H_K10_troglitazone_20uM -0.0193 0.9159 -0.126721 6203.0 troglitazone 20uM PC3 24h
HDAC002_MCF7_24H_F10_PCI-34051_2.5uM -0.0221 0.9194 -0.121294 4791.0 PCI-34051 2.5uM MCF7 24h

International Mouse Phenotyping Consortium (IMPC)

https://www.mousephenotype.org/

IMPC contains serves mouse phenotype information associated with gene markers. Its API is described here and allows us to identify phenotypes significantly associated with a gene.

decreased circulating iron levelcorneal opacityhyperactivityincreased blood uric acid leveldecreased circulating glucose levelvertebral fusionimpaired pupillary reflexdecreased sacral vertebrae numberincreased lumbar vertebrae numberdecreased hemoglobin contentdecreased mean corpuscular hemoglobin024681012141618
Phenotype known to be associated with ASXL1 from IMPC-logp(combined_stouffer_statistic)mp_term_name
/usr/local/lib/python3.8/dist-packages/pandas/core/arraylike.py:397: RuntimeWarning: divide by zero encountered in log10

  result = getattr(ufunc, method)(*inputs, **kwargs)

GlyGen

https://www.glygen.org/

GlyGen collects extensive protein product information related to Glycans and permits accessing that information over their API.

/usr/local/lib/python3.8/dist-packages/urllib3/connectionpool.py:1043: InsecureRequestWarning:



Unverified HTTPS request is being made to host 'api.glygen.org'. Adding certificate verification is strongly advised. See: https://urllib3.readthedocs.io/en/1.26.x/advanced-usage.html#ssl-warnings



No information for gene with identifier ASXL1 found in GlyGen

exRNA

https://ldh.clinicalgenome.org/ldh/ui/

The exRNA Linked Data Hub (LDH) facilitates efficient access to collated information such as links and select data from different data sources, which are made available using RESTful APIs. Currently, LDH focuses on linking information about human genes and variants to support exRNA curation efforts.

We provide the gene symbol to exRNA and obtain the reported linked data. The query will produce a document with all associated regulatory element in the +/- 10kb range or overlapping the gene.

{
    "data": {9 items},
    "metadata": {1 item},
    "status": {2 items}
}

HuBMAP

https://hubmapconsortium.org/

The goal of the Human BioMolecular Atlas Program (HuBMAP) is to develop an open and global platform to map healthy cells in the human body.

The HuBMAP ASCT+B Data was processed and is served by Enrichr. This data can be used to associate genes with cell types.

No information for gene with identifier ASXL1 found in HuBMAP ASCT+B

Metabolomics

https://metabolomicsworkbench.org/

The National Institutes of Health (NIH) Common Fund Metabolomics Program was developed with the goal of increasing national capacity in metabolomics by supporting the development of next generation technologies, providing training and mentoring opportunities, increasing the inventory and availability of high quality reference standards, and promoting data sharing and collaboration.

MetGENE identifies the pathways and reactions catalyzed by the given gene ASXL1, its related metabolites and the studies in Metabolomics Workbench with data on such metabolites.


Secondary Information

Each DCC has assembled a large repository of knowledge besides the data directly collected by the data generation centers they coordinate. We can access this expanded knowledge as well.

IDG

https://druggablegenome.net/

Pharos

We query IDG's knowledge base of targets and their Disease associations through the Pharos API.

Bohring syndromeBohring-Opitz syndromeCraniosynostosesJuvenile Myelomonocytic LeukemiaLeukemia, juvenile myelomonocyticMedulloblastomaMyelodysplastic SyndromeMyelodysplastic syndromeNeoplasm Recurrence, Localacute promyelocytic leukemiacraniosynostosismedulloblastomanephroblastomaoligodendrogliomaependymoma02468101214
Disease known to be associated with ASXL1 from IDG's Pharos-logp(combined_stouffer_statistic)name

Harmonizome

We query the Harmonizome API for associations with various biological entities in a standardized set of numerous omics datasets, as detailed here.

{
    "symbol": "ASXL1",
    "synonyms": [1 item],
    "name": "additional sex combs like transcriptional regulator 1",
    "description": "This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]",
    "ncbiEntrezGeneId": 171023,
    "ncbiEntrezGeneUrl": "http://www.ncbi.nlm.nih.gov/gene/171023",
    "proteins": [1 item],
    "hgncRootFamilies": [],
    "associations": [6066 items]
}
BRD-K36376229/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesZM-226600/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K79604175/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K96979108/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-A17120244/LINCS L1000 CMAP Chemical Perturbation Consensus Signaturessodium-phenylacetate/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K51398207/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K45683404/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K68149575/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-K74095559/LINCS L1000 CMAP Chemical Perturbation Consensus Signatures024681012141618BRD-K17065706/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesBRD-A40022950/LINCS L1000 CMAP Chemical Perturbation Consensus SignaturesLPS141/DepMap CRISPR Gene DependencyRVH421/DepMap CRISPR Gene DependencyLNCAPCLONEFGC/DepMap CRISPR Gene DependencyP2URK562/DepMap CRISPR Gene DependencySNU1544/DepMap CRISPR Gene DependencyGTEx Blood 20-29 vs 60-69/GTEx Tissue-Specific Aging SignaturesJMSU1_URINARY_TRACT/CCLE Cell Line ProteomicsHEC1B/DepMap CRISPR Gene Dependency
directionupdownSignificant associations with ASXL1 in IDG's HarmonizomeabsoluteZscorenamenamedirection=downdirection=up

ARCHS4

https://maayanlab.cloud/archs4/

ARCHS4 has processed numerous GEO studies and also has Tissue expression data.

UnitProt

https://www.uniprot.org/

UniProt is a comprehensive database on protein function information. Their Proteins REST API, documented here, can be used for gene-centric queries.

https://www.ebi.ac.uk/proteins/api/genecentric?offset=0&size=100&gene=STAT3