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Generating Mutational Spectra

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Yo Akiyama edited this page Jun 27, 2023 · 4 revisions

Generating Mutational Spectra

Generating mutational signatures using signatureanalyzer. For a comprehensive description of mutational signatures, their relevance, and references, please see the Catalogue of Somatic Mutations in Cancer, or COSMIC, here, as well as The repertoire of mutational signatures in human cancer. The following document is a reference for easy creation of spectra using .mafs.

Load Mutational Annotation File (maf)

For more information about the .maf format, see here. The following examples show generating mutational spectra from an hg19 .maf using signatureanalyzer. First, load your maf as a pandas dataframe.

The following columns are required:

  • Tumor_Sample_Barcode
  • Chromosome
  • Start_Position
  • Reference_Allele
  • Tumor_Seq_Allele2
  • Variant_Type

The following columns are optional:

  • ref_context: will map context if not provided
import signatureanalyzer as sa
import pandas as pd

maf_df = pd.read_csv(<PATH_TO_MAF>, sep='\t').loc[:,[
  'Hugo_Symbol',
  'Tumor_Sample_Barcode',
  'Chromosome',
  'Start_Position',
  'Reference_Allele',
  'Tumor_Seq_Allele2',
  'Variant_Type'
  ]]

print(maf_df.head())
Hugo_Symbol Tumor_Sample_Barcode Chromosome Start_Position Reference_Allele Tumor_Seq_Allele2 Variant_Type
0 URGCP sample_192 7 43916856 C A SNP
1 CLCN1 sample_127 7 143048832 C A SNP
2 NAV2 sample_354 11 20113762 A G SNP
3 TUBB8P7 sample_32 16 90162224 G T SNP
... CHFR sample_35 12 133438086 C A SNP

Single-base-substitution (SBS) spectra

  • This encodes the 96-base context
  • note: two forms of this exist - either input should work
    • word: ACAG --> (REF)(MUT)(LEFT NT)(RIGHT NT)
    • arrow: A[A>C]G --> (LEFT NT)(REF)>(MUT)(RIGHT NT)
  • REQUIRES a 2-bit human genome build
_,spectra_sbs = sa.spectra.get_spectra_from_maf(maf_df, reference='cosmic3_exome', hgfile='hg19.2bit')

print(spectra_sbs.head().iloc[:,:5])

Arrow

sample_551 sample_135 sample_118 sample_191 sample_124
A[A>C]A 1 2 0 1 2
A[A>C]C 0 2 0 0 0
A[A>C]G 0 6 2 2 0
A[A>C]T 0 4 0 0 2
... 1 2 0 1 0

or

Word

context96.word sample_551 sample_135 sample_118 sample_191 sample_124
ACAA 1 2 0 1 2
ACAC 0 2 0 0 0
ACAG 0 6 2 2 0
ACAT 0 4 0 0 2
... 1 2 0 1 0

Doublet-base-substitution (DBS) spectra

  • This encodes the 78-base context
_,spectra_dbs = sa.spectra.get_spectra_from_maf(maf_df, reference='cosmic3_DBS')

print(spectra_dbs.head())
context78.word sample_0 sample_1 sample_2 sample_3 sample_4
AC>CA 0 0 0 0 0
AC>CG 0 0 0 0 0
AC>CT 0 0 0 0 0
AC>GA 0 0 0 0 0
... 0 0 0 0 0

Insertions & Deletions (ID) spectra

  • This encodes the 83-base context
  • REQUIRES a 2-bit human genome build
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='cosmic3_ID', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context83.word sample_0 sample_1 sample_2 sample_3 sample_4
Cdel1 0 1 3 1 0
Cdel2 0 4 3 6 0
Cdel3 2 2 2 9 0
Cdel4 0 0 0 3 0
... 0 0 1 3 0

Single-base-substitution (SBS) 1536-pentanucleotide spectra

  • This encodes the 1536-base context
  • note: two forms of this exist - either input should work
    • word: ACAGAT --> (REF)(MUT)(L-2)(L-1)(R+1)(R+2)
    • arrow: AA[A>C]GT --> (L-2)(L-1)(REF)>(ALT)(R+2)
  • REQUIRES a 2-bit human genome build
_,spectra_sbs = sa.spectra.get_spectra_from_maf(maf_df, reference='pcawg_SBS', hgfile='hg19.2bit')

print(spectra_sbs.head().iloc[:,:5])

Arrow

sample_551 sample_135 sample_118 sample_191 sample_124
AA[T>A]AA 1 2 0 1 2
AA[T>A]AC 0 2 0 0 0
AA[T>A]AG 0 6 2 2 0
AA[T>A]AT 0 4 0 0 2
... 1 2 0 1 0

or

Word

context1536.word sample_551 sample_135 sample_118 sample_191 sample_124
TAAAAA 1 2 0 1 2
TAAAAC 0 2 0 0 0
TAAAAG 0 6 2 2 0
TAAAAT 0 4 0 0 2
... 1 2 0 1 0

PCAWG Composite spectra

  • This encodes the 1536-base + 78-base + 83-base context
  • REQUIRES a 2-bit human genome build
  • Either SBS form should work (Arrow vs Word)
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='pcawg_COMPOSITE', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
AA[T>A]AA 0 1 3 1 0
AA[T>A]AC 0 4 3 6 0
AA[T>A]AG 2 2 2 9 0
AA[T>A]AT 0 0 0 3 0
... 0 0 0 0 0
AC>CA 0 0 0 3 0
AC>CG 0 0 0 3 0
... 0 0 1 3 0
Cdel1 0 1 3 1 0
Cdel2 0 4 3 6 0
Cdel3 2 2 2 9 0
Cdel4 0 0 0 3 0
... 0 0 1 3 0

PCAWG Composite 96 spectra

  • This encodes the 96-base + 78-base + 83-base context
  • REQUIRES a 2-bit human genome build
  • Either SBS form should work (Arrow vs Word)
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='pcawg_COMPOSITE96', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
A[C>A]A 0 1 3 1 0
A[C>A]C 0 4 3 6 0
A[C>A]G 2 2 2 9 0
A[C>A]T 0 0 0 3 0
... 0 0 0 0 0
AC>CA 0 0 0 3 0
AC>CG 0 0 0 3 0
... 0 0 1 3 0
Cdel1 0 1 3 1 0
Cdel2 0 4 3 6 0
Cdel3 2 2 2 9 0
Cdel4 0 0 0 3 0
... 0 0 1 3 0

PCAWG SBS + ID spectra

  • This encodes the 1536-base + 83-base context
  • REQUIRES a 2-bit human genome build
  • Either SBS form should work (Arrow vs Word)
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='pcawg_SBS_ID', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
AA[T>A]AA 0 1 3 1 0
AA[T>A]AC 0 4 3 6 0
AA[T>A]AG 2 2 2 9 0
AA[T>A]AT 0 0 0 3 0
... 0 0 1 3 0
Cdel1 0 1 3 1 0
Cdel2 0 4 3 6 0
Cdel3 2 2 2 9 0
Cdel4 0 0 0 3 0
... 0 0 1 3 0

PCAWG 96 SBS + ID spectra

  • This encodes the 96-base + 83-base context
  • REQUIRES a 2-bit human genome build
  • Either SBS form should work (Arrow vs Word)
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='pcawg_SBS96_ID', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
A[C>A]A 0 1 3 1 0
A[C>A]C 0 4 3 6 0
A[C>A]G 2 2 2 9 0
A[C>A]T 0 0 0 3 0
... 0 0 0 0 0
Cdel1 0 1 3 1 0
Cdel2 0 4 3 6 0
Cdel3 2 2 2 9 0
Cdel4 0 0 0 3 0
... 0 0 1 3 0

POLE/POLD-exo* + MSI 1536 SBS + ID spectra

  • This encodes the 1536-base + 8-base context
  • REQUIRES a 2-bit human genome build
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='polymerase_msi', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
AA[T>A]AA 0 1 3 1 0
AA[T>A]AC 0 4 3 6 0
AA[T>A]AG 2 2 2 9 0
AA[T>A]AT 0 0 0 3 0
... 0 0 1 3 0
INS4 0 1 3 1 0
DEL1 0 4 3 6 0
DEL3 2 2 2 9 0
DEL4 0 0 0 3 0

POLE/POLD-exo* + MSI 96 SBS + ID spectra

  • This encodes the 1536-base + 8-base context
  • REQUIRES a 2-bit human genome build
_,spectra_id = sa.spectra.get_spectra_from_maf(maf_df, reference='polymerase_msi96', hgfile='hg19.2bit')

print(spectra_id.head().iloc[:,:5])
context.pcawg sample_0 sample_1 sample_2 sample_3 sample_4
A[C>A]A 0 1 3 1 0
A[C>A]C 0 4 3 6 0
A[C>A]G 2 2 2 9 0
A[C>A]T 0 0 0 3 0
... 0 0 1 3 0
INS4 0 1 3 1 0
DEL1 0 4 3 6 0
DEL3 2 2 2 9 0
DEL4 0 0 0 3 0
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