Curate entity identifiers

To make data queryable by an entity identifier, one needs to ensure that identifiers comply to a chosen standard. Bionty enables this by curating data against the versionized ontologies using curate().

We’ll demonstrate this by first curating genes and second CellMarkers where not all values can be immediately mapped.

Let’s start by importing the required modules from Bionty and Pandas.

from bionty import Gene, CellMarker
import pandas as pd

/home/runner/work/bionty/bionty/.nox/build-package-bionty/lib/python3.9/site-packages/tqdm/auto.py:21: TqdmWarning: IProgress not found. Please update jupyter and ipywidgets. See https://ipywidgets.readthedocs.io/en/stable/user_install.html
  from .autonotebook import tqdm as notebook_tqdm

Curating genes

To illustrate it, let us generate a DataFrame that stores a number of gene identifiers, some of which corrupted.

data = {
    "gene symbol": ["A1CF", "A1BG", "FANCD1", "corrupted"],
    "hgnc id": ["HGNC:24086", "HGNC:5", "HGNC:1101", "corrupted"],
    "ensembl_gene_id": [
        "ENSG00000148584",
        "ENSG00000121410",
        "ENSG00000188389",
        "corrupted",
    ],
}
df_orig = pd.DataFrame(data).set_index("ensembl_gene_id")

df_orig

	gene symbol	hgnc id
ensembl_gene_id
ENSG00000148584	A1CF	HGNC:24086
ENSG00000121410	A1BG	HGNC:5
ENSG00000188389	FANCD1	HGNC:1101
corrupted	corrupted	corrupted

We require a reference identifier (specified as the reference_id parameter for curate). The list can be looked up using lookup(). Examples are “ontology_id”, which corresponds to the IDs of the ontology terms (e.g. ‘ENSG00000148584’) or “name” which corresponds to the ontology term names (e.g. ‘A1CF’).

To curate the DataFrame into queryable form, we create an index that corresponds to a default identifier. By default we use ensembl_gene_id. The default behavior is to curate the index if a column name is not provided.

First we create a Gene() instance using the default source database and version.

gene = Gene()

First we can check whether any of our values are mappable against the ontology.

gene.inspect(df_orig.index, reference_id=gene.ensembl_gene_id)

✅ 3 terms (75.0%) are mapped.

🔶 1 terms (25.0%) are not mapped.

{'mapped': ['ENSG00000148584', 'ENSG00000121410', 'ENSG00000188389'],
 'not_mapped': ['corrupted']}

We have identified 3 terms that are mappable against the Ontology. Let’s curate them by mapping them against the ontology. By default, Bionty uses the index column if not specified otherwise.

gene.curate(df_orig)

✅ 3 terms (75.0%) are mapped.

🔶 1 terms (25.0%) are not mapped.

	gene symbol	hgnc id	orig_index	__curated__
ensembl_gene_id
ENSG00000148584	A1CF	HGNC:24086	ENSG00000148584	True
ENSG00000121410	A1BG	HGNC:5	ENSG00000121410	True
ENSG00000188389	FANCD1	HGNC:1101	ENSG00000188389	True
corrupted	corrupted	corrupted	corrupted	False

The curated DataFrame has now been reindexed by the curated cell types. A new column orig_index containing the original index has been added. Furthermore, a new column __curated__ containing booleans of whether the data could be successfully curated or not has been added.

The same procedure is available for gene symbols. First, we inspect which symbols are mappable against the ontology.

gene.inspect(df_orig["gene symbol"], reference_id=gene.symbol)

🔶 The identifiers contain synonyms!

💡 To increase mappability, convert them into standardized names/symbols using '.map_synonyms()'

✅ 2 terms (50.0%) are mapped.

🔶 2 terms (50.0%) are not mapped.

{'mapped': ['A1CF', 'A1BG'], 'not_mapped': ['FANCD1', 'corrupted']}

Apparently 2 of the gene symbols are mappable. Bionty further warns us that some of our symbols can be mapped into standardized symbols.

mapped_symbol_synonyms = gene.map_synonyms(
    df_orig["gene symbol"], reference_id=gene.symbol
)
mapped_symbol_synonyms

['A1CF', 'A1BG', 'BRCA2', 'corrupted']

We can store them in our DataFrame further use.

df_orig["non-synonymous gene symbol"] = mapped_symbol_synonyms

You may provide a column name to curate a specific column against a reference identifier. When mapping symbols, the function will automatically convert the aliases into standardized symbols. In this example, FANCD1 is converted into BRACA2.

gene.curate(df_orig, column="gene symbol", reference_id=gene.symbol)

✅ 3 terms (75.0%) are mapped.

🔶 1 terms (25.0%) are not mapped.

	gene symbol	hgnc id	non-synonymous gene symbol	ensembl_gene_id	__curated__
symbol
13736.0	A1CF	HGNC:24086	A1CF	ENSG00000148584	True
24881.0	A1BG	HGNC:5	A1BG	ENSG00000121410	True
17731.0	FANCD1	HGNC:1101	BRCA2	ENSG00000188389	True
corrupted	corrupted	corrupted	corrupted	corrupted	False

This is synonymous to:

gene.curate(df_orig, column="gene symbol", reference_id=gene.symbol)

✅ 3 terms (75.0%) are mapped.

🔶 1 terms (25.0%) are not mapped.

	gene symbol	hgnc id	non-synonymous gene symbol	ensembl_gene_id	__curated__
symbol
13736.0	A1CF	HGNC:24086	A1CF	ENSG00000148584	True
24881.0	A1BG	HGNC:5	A1BG	ENSG00000121410	True
17731.0	FANCD1	HGNC:1101	BRCA2	ENSG00000188389	True
corrupted	corrupted	corrupted	corrupted	corrupted	False

Of course this also works with other columns such as “hgnc id”.

gene.curate(df_orig, column="hgnc id", reference_id=gene.hgnc_id)

✅ 3 terms (75.0%) are mapped.

🔶 1 terms (25.0%) are not mapped.

	gene symbol	hgnc id	non-synonymous gene symbol	ensembl_gene_id	__curated__
hgnc_id
13736.0	A1CF	HGNC:24086	A1CF	ENSG00000148584	True
24881.0	A1BG	HGNC:5	A1BG	ENSG00000121410	True
17731.0	FANCD1	HGNC:1101	BRCA2	ENSG00000188389	True
corrupted	corrupted	corrupted	corrupted	corrupted	False

Match (unmappable) cell markers to the reference

Depending on how the data was collected and which terminology was used, it is not always possible to curate the values. Some values might have used a different standard or are simply corrupted.

This section will demonstrate how to look up unmatched terms and curating them using The CellMarker entity. First, we create an example Pandas DataFrame containing a few valid and invalid cell markers (antibody targets) and features (Time) from a flow cytometry dataset.

markers = pd.DataFrame(
    index=[
        "KI67",
        "CCR7x",
        "CD14",
        "CD8",
        "CD45RA",
        "CD4",
        "CD3",
        "CD127",
        "PD1",
        "Invalid-1",
        "Invalid-2",
        "CD66b",
        "Siglec8",
        "Time",
    ]
)

Let’s instantiate the CellMarker ontology with the default database and version.

cell_marker = CellMarker()

First, we can have a look at the cell marker table that we just loaded.

df = cell_marker.df()

df.head()

	id	name	ncbi_gene_id	gene_symbol	gene_name	uniprotkb_id	synonyms
0	CM_MERTK	MERTK	10461	MERTK	MER proto-oncogene, tyrosine kinase	Q12866	None
1	CM_CD16	CD16	2215	FCGR3A	Fc fragment of IgG receptor IIIb	O75015	None
2	CM_CD206	CD206	4360	MRC1	mannose receptor C-type 1	P22897	None
3	CM_CRIg	CRIg	11326	VSIG4	V-set and immunoglobulin domain containing 4	Q9Y279	None
4	CM_CD163	CD163	9332	CD163	CD163 molecule	Q86VB7	None

Now let’s check which cell markers from the file can be found in the reference. We do this using the .curate function:

cell_marker.curate(markers)

✅ 10 terms (71.4%) are mapped.

🔶 4 terms (28.6%) are not mapped.

	orig_index	__curated__
Ki67	KI67	True
CCR7x	CCR7x	False
CD14	CD14	True
CD8	CD8	True
CD45RA	CD45RA	True
CD4	CD4	True
CD3	CD3	True
CD127	CD127	True
PD-1	PD1	True
Invalid-1	Invalid-1	False
Invalid-2	Invalid-2	False
CD66b	CD66b	True
SIGLEC8	Siglec8	True
Time	Time	False

From the logging, it can be seen that 4 terms were not found in the reference!

Among them Time, Invalid-1 and Invalid-2 are non-marker channels which won’t be curated by cell marker.

Note, certain markers will be converted to synonyms such as PD1 -> PD-1.

We don’t really find CCR7x, let’s check in the lookup with auto-completion:

cell_marker_lookup = cell_marker.lookup()

cell_marker_lookup.CCR7

cell_marker(index=163, id='CM_CCR7', name='CCR7', ncbi_gene_id='1236', gene_symbol='CCR7', gene_name='C-C motif chemokine receptor 7', uniprotkb_id='P32248', synonyms=None)

Indeed we find it should be CCR7, we had a typo there with CCR7x.

Now let’s fix the markers so all of them can be linked:

Tip

Using the .lookup instead of passing a string helps eliminate possible typos!

curated_df = markers.rename(index={"CCR7x": cell_marker_lookup.CCR7.name})

OK, now we can try to run curate again and all cell markers are linked!

cell_marker.curate(curated_df)

✅ 11 terms (78.6%) are mapped.

🔶 3 terms (21.4%) are not mapped.

	orig_index	__curated__
Ki67	KI67	True
CCR7	CCR7	True
CD14	CD14	True
CD8	CD8	True
CD45RA	CD45RA	True
CD4	CD4	True
CD3	CD3	True
CD127	CD127	True
PD-1	PD1	True
Invalid-1	Invalid-1	False
Invalid-2	Invalid-2	False
CD66b	CD66b	True
SIGLEC8	Siglec8	True
Time	Time	False