Jupyter Notebook

Gene Ontology (GO)

Pathways represent interconnected molecular networks of signaling cascades that govern critical cellular processes. They provide understandings cellular behavior mechanisms, insights of disease progression and treatment responses. In an R&D organization, managing pathways across different datasets are crucial for gaining insights of potential therapeutic targets and intervention strategies.

In this notebook we manage a pathway registry based on “2023 GO Biological Process” ontology. We’ll walk you through the steps of registering pathways and link them to genes.

In the following Standardize metadata on-the-fly notebook, we’ll demonstrate how to perform a pathway enrichment analysis and track the dataset with LaminDB.

# !pip install 'lamindb[jupyter,bionty]'
!lamin init --storage ./use-cases-registries --modules bionty
Hide code cell output
 initialized lamindb: testuser1/use-cases-registries
import lamindb as ln
import bionty as bt
import gseapy as gp

bt.settings.organism = "human"  # globally set organism
 connected lamindb: testuser1/use-cases-registries

Fetch GO pathways annotated with human genes using Enrichr

First we fetch the “GO_Biological_Process_2023” pathways for humans using GSEApy which wraps GSEA and Enrichr.

go_bp = gp.get_library(name="GO_Biological_Process_2023", organism="Human")
print(f"Number of pathways {len(go_bp)}")
Number of pathways 5406
go_bp["ATF6-mediated Unfolded Protein Response (GO:0036500)"]
['MBTPS1', 'MBTPS2', 'XBP1', 'ATF6B', 'DDIT3', 'CREBZF']

Parse out the ontology_id from keys, convert into the format of {ontology_id: (name, genes)}

def parse_ontology_id_from_keys(key):
    """Parse out the ontology id.

    "ATF6-mediated Unfolded Protein Response (GO:0036500)" -> ("GO:0036500", "ATF6-mediated Unfolded Protein Response")
    """
    name, id = key.rsplit(" (", 1)
    id = id.rstrip(")")
    return id, name
go_bp_parsed = {}

for key, genes in go_bp.items():
    id, name = parse_ontology_id_from_keys(key)
    go_bp_parsed[id] = (name, genes)
go_bp_parsed["GO:0036500"]
('ATF6-mediated Unfolded Protein Response',
 ['MBTPS1', 'MBTPS2', 'XBP1', 'ATF6B', 'DDIT3', 'CREBZF'])

Register pathway ontology in LaminDB

bionty = bt.Pathway.public()
bionty
Hide code cell output
PublicOntology
Entity: Pathway
Organism: all
Source: go, 2024-06-17
#terms: 47856

Next, we register all the pathways and genes in LaminDB to finally link pathways to genes.

Register pathway terms

To register the pathways we make use of .from_values to directly parse the annotated GO pathway ontology IDs into LaminDB.

pathway_records = bt.Pathway.from_values(go_bp_parsed.keys(), bt.Pathway.ontology_id)
ln.save(pathway_records)

Register gene symbols

Similarly, we use .from_values for all Pathway associated genes to register them with LaminDB.

all_genes = bt.Gene.standardize(list({g for genes in go_bp.values() for g in genes}))
gene_records = bt.Gene.from_values(all_genes, bt.Gene.symbol)
ln.save(gene_records);
! found 56 synonyms in public source (output truncated): [np.str_('C3ORF38'), np.str_('USP41'), np.str_('C10ORF90'), np.str_('C3ORF70'), np.str_('C8ORF17'), np.str_('C8ORF88'), np.str_('C12ORF4'), np.str_('RNF165'), np.str_('C1ORF43'), np.str_('PIFO'), '...']
  please add corresponding Gene records via (output truncated): `.from_values([np.str_('C3ORF38'), np.str_('USP41'), np.str_('C10ORF90'), np.str_('C3ORF70'), np.str_('C8ORF17'), np.str_('C8ORF88'), np.str_('C12ORF4'), np.str_('RNF165'), np.str_('C1ORF43'), np.str_('PIFO'), '...'])`
! ambiguous validation in Bionty for 1104 records: 'OR2H1', 'PLEKHA8P1', 'ADAMTS12', 'GART', 'ASF1B', 'APBA1', 'PARP2', 'CTIF', 'TRIM15', 'OR2A12', 'TPRXL', 'PANK4', 'ZNF598', 'TAS2R46', 'PCDHB4', 'TSEN34', 'FAM86B1', 'ABCC6', 'OR10J1', 'OR2T5', ...
! did not create Gene records for 38 non-validated symbols: 'AFD1', 'AZF1', 'CCL3L1', 'CCL4L1', 'DGS2', 'DUX3', 'DUX5', 'FOXL3-OT1', 'IGL', 'LOC100653049', 'LOC102723475', 'LOC102723996', 'LOC102724159', 'LOC107984156', 'LOC112268384', 'LOC122319436', 'LOC122513141', 'LOC122539214', 'LOC344967', 'MDRV', ...

Manually register the 37 non-validated symbols:

inspect_result = bt.Gene.inspect(all_genes, bt.Gene.symbol)

nonval_genes = []
for g in inspect_result.non_validated:
    nonval_genes.append(bt.Gene(symbol=g))

ln.save(nonval_genes)
! received 14696 unique terms, 1 empty/duplicated term is ignored
! 38 unique terms (0.30%) are not validated for symbol: 'MTRNR2L13', 'LOC344967', 'TAS2R36', 'TRL-AAG2-3', 'TAS2R33', 'MTRNR2L6', 'FOXL3-OT1', 'MTRNR2L4', 'MTRNR2L2', 'LOC122513141', ...
   couldn't validate 38 terms: 'MTRNR2L9', 'CCL3L1', 'MTRNR2L5', 'LOC107984156', 'TRA', 'LOC112268384', 'DGS2', 'DUX5', 'TRL-AAG2-3', 'LOC344967', 'AFD1', 'MTRNR2L8', 'MTRNR2L11', 'SEPTIN14P20', 'TAS2R36', 'MTRNR2L3', 'LOC122539214', 'MTRNR2L13', 'LOC122319436', 'MTRNR2L4', ...
→  if you are sure, create new records via Gene() and save to your registry
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
184 5oVzvf9oqvpN TAS2R46 None ENSG00000226761 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
185 7HDTaG63CsMc TAS2R46 None ENSG00000262525 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
186 1TwUNC8vghgg TAS2R46 None ENSG00000278111 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
184 5oVzvf9oqvpN TAS2R46 None ENSG00000226761 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
185 7HDTaG63CsMc TAS2R46 None ENSG00000262525 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
186 1TwUNC8vghgg TAS2R46 None ENSG00000278111 259292 protein_coding T2R54 taste 2 receptor member 46 1 11 1 None 2025-03-31 12:36:10.176000+00:00 1 None 1
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
4747 7TBpxi4zzmMB IGLC3 None ENSG00000211679 IG_C_gene IGLC immunoglobulin lambda constant 3 (Kern-Oz+ mar... 1 11 1 None 2025-03-31 12:36:10.552000+00:00 1 None 1
5491 10LbfkUokHgx IGLC1 None ENSG00000211675 IG_C_gene IGLC immunoglobulin lambda constant 1 1 11 1 None 2025-03-31 12:36:10.616000+00:00 1 None 1
6302 2qFUCnrrxPlc IGLC7 None ENSG00000211685 IG_C_gene immunoglobulin lambda constant 7 1 11 1 None 2025-03-31 12:36:10.866000+00:00 1 None 1
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
236 3vSQURO6QTSd TRAF5 None ENSG00000082512 7188 protein_coding RNF84 TNF receptor associated factor 5 1 11 1 None 2025-03-31 12:36:10.181000+00:00 1 None 1
427 5XEaSvGuBHGd TRA2B None ENSG00000136527 6434 protein_coding SFRS10|PPP1R156|HTRA2-BETA transformer 2 beta homolog 1 11 1 None 2025-03-31 12:36:10.195000+00:00 1 None 1
733 4aXWpkO7oC2T TRAPPC8 None ENSG00000153339 22878 protein_coding GSG1|KIAA1012|HST2706|TRS85 trafficking protein particle complex subunit 8 1 11 1 None 2025-03-31 12:36:10.218000+00:00 1 None 1
! record with similar symbol exists! did you mean to load it?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
1300 2Z2LBAj16utl TRAFD1 None ENSG00000135148 10906 protein_coding FLN29 TRAF-type zinc finger domain containing 1 1 11 1 None 2025-03-31 12:36:10.264000+00:00 1 None 1
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
10410 TfqHfw8FjZxq CCL4 None ENSG00000275302 6351 protein_coding MIP-1-BETA|SCYA4|AT744.1|LAG1|ACT-2 C-C motif chemokine ligand 4 1 11 1 None 2025-03-31 12:36:11.220000+00:00 1 None 1
10411 2MLaX8EEZ9sQ CCL4 None ENSG00000275824 6351 protein_coding MIP-1-BETA|SCYA4|AT744.1|LAG1|ACT-2 C-C motif chemokine ligand 4 1 11 1 None 2025-03-31 12:36:11.220000+00:00 1 None 1
10412 7P74Aze5sMxb CCL4 None ENSG00000277943 6351 protein_coding MIP-1-BETA|SCYA4|AT744.1|LAG1|ACT-2 C-C motif chemokine ligand 4 1 11 1 None 2025-03-31 12:36:11.220000+00:00 1 None 1
! record with similar symbol exists! did you mean to load it?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
4135 217N4Hgazwqu JAZF1 None ENSG00000153814 221895 protein_coding TIP27|ZNF802|DKFZP761K2222 JAZF zinc finger 1 1 11 1 None 2025-03-31 12:36:10.499000+00:00 1 None 1
! records with similar symbols exist! did you mean to load one of them?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
15502 F36vWNagki41 CCL3 None ENSG00000274221 6348 protein_coding LD78|G0S19-1|SCYA3|LD78ALPHA|SCI|MIP-1-ALPHA C-C motif chemokine ligand 3 1 11 1 None 2025-03-31 12:36:11.831000+00:00 1 None 1
15503 EBoWJxh70guC CCL3 None ENSG00000277632 6348 protein_coding LD78|G0S19-1|SCYA3|LD78ALPHA|SCI|MIP-1-ALPHA C-C motif chemokine ligand 3 1 11 1 None 2025-03-31 12:36:11.831000+00:00 1 None 1
15504 6XmKAksx3Nn4 CCL3 None ENSG00000278567 6348 protein_coding LD78|G0S19-1|SCYA3|LD78ALPHA|SCI|MIP-1-ALPHA C-C motif chemokine ligand 3 1 11 1 None 2025-03-31 12:36:11.831000+00:00 1 None 1
! record with similar symbol exists! did you mean to load it?
uid symbol stable_id ensembl_gene_id ncbi_gene_ids biotype synonyms description space_id source_id organism_id run_id created_at created_by_id _aux _branch_code
id
13890 19ZTVOfazMYF SEPTIN14 None ENSG00000154997 346288 protein_coding SEPT14|FLJ44060 septin 14 1 11 1 None 2025-03-31 12:36:11.688000+00:00 1 None 1