GencodeGeneRepository — exploración¶

Carga todos los genes con sus transcritos desde el GFF3 de GENCODE v49 (GRCh38).
El repositorio se instancia una sola vez vía get_gencode_repo() (singleton con @cache).

In [1]:

%load_ext autoreload
%autoreload 2

%load_ext autoreload %autoreload 2

In [2]:

import time
from collections import Counter
from functools import cache
from pathlib import Path

from iris.adapters.driven.readers.providers.gencode import GencodeGeneRepository

GFF3_PATH = Path(
    "/mnt/cephfs/hot_nvme/gencode/GRCh38.14/gencode.v49.basic.annotation.gff3.gz"
)

import time from collections import Counter from functools import cache from pathlib import Path from iris.adapters.driven.readers.providers.gencode import GencodeGeneRepository GFF3_PATH = Path( "/mnt/cephfs/hot_nvme/gencode/GRCh38.14/gencode.v49.basic.annotation.gff3.gz" )

Singleton¶

@cache garantiza que el archivo se lea solo una vez por sesión del kernel, aunque la celda se re-ejecute.

In [3]:

@cache
def get_gencode_repo() -> GencodeGeneRepository:
    return GencodeGeneRepository(
        GFF3_PATH,
        assembly="GRCh38",
        version="v49",
    )

@cache def get_gencode_repo() -> GencodeGeneRepository: return GencodeGeneRepository( GFF3_PATH, assembly="GRCh38", version="v49", )

Carga inicial¶

La primera llamada dispara la lectura del GFF3 y construye el índice en memoria.

In [4]:

t0 = time.time()
repo = get_gencode_repo()
all_annotations = repo.find_all_annotations()
elapsed = time.time() - t0

print(f"Genes cargados : {len(all_annotations):,}")
print(f"Tiempo         : {elapsed:.1f}s")

t0 = time.time() repo = get_gencode_repo() all_annotations = repo.find_all_annotations() elapsed = time.time() - t0 print(f"Genes cargados : {len(all_annotations):,}") print(f"Tiempo : {elapsed:.1f}s")

Genes cargados : 78,691
Tiempo         : 131.6s

Estadísticas generales¶

In [5]:

n_transcripts = sum(len(a.transcripts) for a in all_annotations)
biotype_counts = Counter(a.biotype.name for a in all_annotations)
tr_per_gene = [len(a.transcripts) for a in all_annotations]

print(f"Transcritos totales : {n_transcripts:,}")
print(
    f"Transcritos/gen     : media={sum(tr_per_gene)/len(tr_per_gene):.1f}  max={max(tr_per_gene)}"
)
print()
print("Biotipos (top 10):")
for biotype, n in biotype_counts.most_common(10):
    print(f"  {biotype:<35} {n:>8,}")

n_transcripts = sum(len(a.transcripts) for a in all_annotations) biotype_counts = Counter(a.biotype.name for a in all_annotations) tr_per_gene = [len(a.transcripts) for a in all_annotations] print(f"Transcritos totales : {n_transcripts:,}") print( f"Transcritos/gen : media={sum(tr_per_gene)/len(tr_per_gene):.1f} max={max(tr_per_gene)}" ) print() print("Biotipos (top 10):") for biotype, n in biotype_counts.most_common(10): print(f" {biotype:<35} {n:>8,}")

Transcritos totales : 280,000
Transcritos/gen     : media=3.6  max=346

Biotipos (top 10):
  NON_CODING                            41,946
  PROTEIN_CODING                        20,097
  PSEUDOGENE                            14,464
  TEC                                    1,019
  IMMUNE_RECEPTOR                          648
  OTHER                                    517

Búsqueda por gen¶

In [6]:

ann = repo.get_annotation("BRCA1")
assert ann is not None

g = ann.gene
print(f"Símbolo   : {g.symbol}")
print(f"Posición  : {g.position}")
print(f"Biotipo   : {ann.biotype.name}")
print(f"Transcritos: {len(ann.transcripts)}")

ann = repo.get_annotation("BRCA1") assert ann is not None g = ann.gene print(f"Símbolo : {g.symbol}") print(f"Posición : {g.position}") print(f"Biotipo : {ann.biotype.name}") print(f"Transcritos: {len(ann.transcripts)}")

Símbolo   : BRCA1
Posición  : GenomicPosition(chromosome='17', assembly='GRCh38', start=43044292, end=43170245, strand=<Strand.MINUS: '-'>, name=None, markers=())
Biotipo   : PROTEIN_CODING
Transcritos: 32

Transcritos MANE Select¶

In [7]:

mane_select = [
    (a.gene.symbol, t)
    for a in all_annotations
    for t in a.transcripts
    if t.is_mane_select
]

print(f"Transcritos MANE Select: {len(mane_select):,}")
print()
print("Ejemplos:")
for symbol, t in mane_select[:10]:
    n_exons = len(t.exons)
    n_cds = len(t.cds)
    print(f"  {symbol:<12}  {t.name:<20}  exones={n_exons:>3}  CDS={n_cds:>3}")

mane_select = [ (a.gene.symbol, t) for a in all_annotations for t in a.transcripts if t.is_mane_select ] print(f"Transcritos MANE Select: {len(mane_select):,}") print() print("Ejemplos:") for symbol, t in mane_select[:10]: n_exons = len(t.exons) n_cds = len(t.cds) print(f" {symbol:<12} {t.name:<20} exones={n_exons:>3} CDS={n_cds:>3}")

Transcritos MANE Select: 19,276

Ejemplos:
  OR4F5         ENST00000641515.2     exones=  2  CDS=  2
  OR4F29        ENST00000426406.4     exones=  0  CDS=  0
  OR4F16        ENST00000332831.5     exones=  0  CDS=  0
  SAMD11        ENST00000616016.5     exones= 13  CDS= 14
  NOC2L         ENST00000327044.7     exones= 18  CDS= 19
  KLHL17        ENST00000338591.8     exones= 11  CDS= 12
  PLEKHN1       ENST00000379410.8     exones= 15  CDS= 16
  PERM1         ENST00000433179.4     exones=  3  CDS=  3
  HES4          ENST00000304952.11    exones=  3  CDS=  4
  ISG15         ENST00000649529.1     exones=  1  CDS=  2

Estructura de un transcrito — BRCA1 MANE Select¶

In [8]:

brca1_mane = next(
    (t for t in ann.transcripts if t.is_mane_select),
    ann.transcripts[0],
)

print(f"Transcrito : {brca1_mane.name}")
print(f"Biotipo    : {brca1_mane.biotype.name}")
print(f"Canónico   : {brca1_mane.is_canonical}")
print(f"MANE Select: {brca1_mane.is_mane_select}")
print(f"Posición   : {brca1_mane.position}")
print(f"Exones     : {len(brca1_mane.exons)}")
print(f"CDS        : {len(brca1_mane.cds)}")
print(f"UTRs       : {len(brca1_mane.utrs)}")
print(f"Start codón: {brca1_mane.start_codon}")
print(f"Stop codón : {brca1_mane.stop_codon}")
print()
print("Primeros 5 exones:")
for e in brca1_mane.exons[:5]:
    print(f"  {e}")

brca1_mane = next( (t for t in ann.transcripts if t.is_mane_select), ann.transcripts[0], ) print(f"Transcrito : {brca1_mane.name}") print(f"Biotipo : {brca1_mane.biotype.name}") print(f"Canónico : {brca1_mane.is_canonical}") print(f"MANE Select: {brca1_mane.is_mane_select}") print(f"Posición : {brca1_mane.position}") print(f"Exones : {len(brca1_mane.exons)}") print(f"CDS : {len(brca1_mane.cds)}") print(f"UTRs : {len(brca1_mane.utrs)}") print(f"Start codón: {brca1_mane.start_codon}") print(f"Stop codón : {brca1_mane.stop_codon}") print() print("Primeros 5 exones:") for e in brca1_mane.exons[:5]: print(f" {e}")

Transcrito : ENST00000357654.9
Biotipo    : PROTEIN_CODING
Canónico   : True
MANE Select: True
Posición   : GenomicPosition(chromosome='17', assembly='GRCh38', start=43044295, end=43125364, strand=<Strand.MINUS: '-'>, name=None, markers=())
Exones     : 22
CDS        : 22
UTRs       : 2
Start codón: GenomicPosition(chromosome='17', assembly='GRCh38', start=43124094, end=43124096, strand=<Strand.MINUS: '-'>, name=None, markers=())
Stop codón : GenomicPosition(chromosome='17', assembly='GRCh38', start=43045678, end=43045680, strand=<Strand.MINUS: '-'>, name=None, markers=())

Primeros 5 exones:
  GenomicPosition(chromosome='17', assembly='GRCh38', start=43047643, end=43047703, strand=<Strand.MINUS: '-'>, name='ENSE00004011552.1', markers=())
  GenomicPosition(chromosome='17', assembly='GRCh38', start=43049121, end=43049194, strand=<Strand.MINUS: '-'>, name='ENSE00004011568.1', markers=())
  GenomicPosition(chromosome='17', assembly='GRCh38', start=43051063, end=43051117, strand=<Strand.MINUS: '-'>, name='ENSE00004011553.1', markers=())
  GenomicPosition(chromosome='17', assembly='GRCh38', start=43057052, end=43057135, strand=<Strand.MINUS: '-'>, name='ENSE00004011551.1', markers=())
  GenomicPosition(chromosome='17', assembly='GRCh38', start=43063333, end=43063373, strand=<Strand.MINUS: '-'>, name='ENSE00004011567.1', markers=())

Búsqueda por posición genómica¶

In [9]:

from iris.domain.genomics.objects import GenomicPosition

# Posición conocida en BRCA1 (chr17:43,044,295, 1-based)
pos = GenomicPosition(
    chromosome="chr17", start=43_044_295, end=43_044_295, assembly="GRCh38"
)
genes_at_pos = repo.find_by_position(pos)

print(f"Genes en {pos}: {[g.symbol for g in genes_at_pos]}")

from iris.domain.genomics.objects import GenomicPosition # Posición conocida en BRCA1 (chr17:43,044,295, 1-based) pos = GenomicPosition( chromosome="chr17", start=43_044_295, end=43_044_295, assembly="GRCh38" ) genes_at_pos = repo.find_by_position(pos) print(f"Genes en {pos}: {[g.symbol for g in genes_at_pos]}")

Genes en GenomicPosition(chromosome='chr17', assembly='GRCh38', start=43044295, end=43044295, strand=None, name=None, markers=()): []