Infers the V genotype of an individual from immunoglobulin (Ig)
repertoire sequencing data (AIRR-Seq, Rep-Seq). Includes detection of
any novel alleles. This information is then used to correct existing V
allele calls from among the sample sequences.
Citations:
Gadala-Maria, et al (2015)
High-throughput sequencing of B cell immunoglobulin receptors is providing unprecedented insight into adaptive immunity. A key step in analyzing these data involves assignment of the germline V, D and J gene segment alleles that comprise each immunoglobulin sequence by matching them against a database of known V(D)J alleles. However, this process will fail for sequences that utilize previously undetected alleles, whose frequency in the population is unclear.
TIgGER is a computational method that significantly improves V(D)J allele assignments by first determining the complete set of gene segments carried by an individual (including novel alleles) from V(D)J-rearrange sequences. TIgGER can then infer a subject's genotype from these sequences, and use this genotype to correct the initial V(D)J allele assignments.
The application of TIgGER continues to identify a surprisingly high frequency of novel alleles in humans, highlighting the critical need for this approach. (TIgGER, however, can and has been used with data from other species.)
The former can be created through the use of IMGT/HighV-QUEST and Change-O.
For help, questions, or suggestions, please contact the Immcantation Group or use the issue tracker.
reassignAlleles
with non-existent v_call
column.generateEvidence
that was reporting amino acids mutations as
NA instead of gaps.Bug Fixes:
reassignAlleles
occuring with single match genotypes.selectNovel
improperly removing all identical novel alleles, rather
than keeping a single entry.genotypeFasta
will now retain IMGT-numbering spacers as .
characters
instead of converting them to -
characters.findNovelAlleles
causing overly aggressive minimum sequence
threshold filtering.getPopularMutationCount
.New Features:
inferGenotypeBayesian
function.generateEvidence
to build a complete evidence table
from the results of findNovelAlleles
, inferGenotype
,
inferGenotypeBayesian
, and reassignAlleles
.findNovelAlleles
and adjusted the definitions/names of some existing columns.keep_gene
argument of reassignAlleles
to provide
options for maintaining reassignments at the gene (previous TRUE
behavior),
family, or repertoire level.findNovelAlleles
.Backwards Incompatible Refactors:
germline_ighv
, sample_db
, genotype
and
novel_df
to GermlineIGHV
, SampleDb
, SampleGenotype
and SampleNovel
,
respectively.novel_df
argument to novel
in selectNovel
, inferGenotype
,
and genotypeFasta
.novel_df_row
argument to novel_row
in plotNovel
.inferGenotype
was alter for clarity.reassignAlleles
so that it returns the
input data.frame with the V_CALL_GENOTYPED
column appended or overwritten.cleanSeqs
will no longer replace .
characters with -
.findNovelAlleles
.inferGenotype
would break when performing check for alleles
that could not be distinguished.inferGenotype
would break if all sequences submitted were
from a single gene and find_unmutated
was set to TRUE
.findNovelAlleles()
was not running in parallel, even
when nproc
> 1.nproc=1
in findNovelAlleles()
.