Sequence-based TF affinity scoring can be conducted with the FIMO suite, see @Sonawane2017. We have serialized an object with references to FIMO outputs for 16 TFs.
## GenomicFiles object with 1 ranges and 16 files:
## files: M0635_1.02sort.bed.gz, M3433_1.02sort.bed.gz, ..., M6159_1.02sort.bed.gz, M6497_1.02sort.bed.gz
## detail: use files(), rowRanges(), colData(), ...While the token bed is used in the filenames, the files are
not actually bed format!
scanTabixWe can use reduceByRange to import selected scans.
si = TFutils::seqinfo_hg19_chr17
myg = GRanges("chr17", IRanges(38.07e6,38.09e6), seqinfo=si)
colnames(fimo16) = fimo16$HGNC
lk2 = reduceByRange(fimo16[, c("POU2F1", "VDR")],
MAP=function(r,f) scanTabix(f, param=r))
str(lk2)## List of 1
## $ :List of 2
## ..$ POU2F1:List of 1
## .. ..$ chr17:38077000-38084000: chr [1:12] "chr17\t38077313\t38077331\tchr17:38077313-38077331\t2.15306\t+\t0.000352" "chr17\t38078549\t38078567\tchr17:38078549-38078567\t0.102041\t-\t0.000634" "chr17\t38078556\t38078574\tchr17:38078556-38078574\t-0.0408163\t-\t0.00066" "chr17\t38080045\t38080063\tchr17:38080045-38080063\t1.66327\t-\t0.000407" ...
## ..$ VDR :List of 1
## .. ..$ chr17:38077000-38084000: chr [1:18] "chr17\t38077445\t38077460\tchr17:38077445-38077460\t-1.9899\t-\t0.000666" "chr17\t38078536\t38078551\tchr17:38078536-38078551\t-2.66667\t-\t0.0008" "chr17\t38078574\t38078589\tchr17:38078574-38078589\t1.65657\t+\t0.000235" "chr17\t38078796\t38078811\tchr17:38078796-38078811\t2.07071\t-\t0.000207" ...This result can be massaged into a GRanges or other desirable structure.
fimo_granges takes care of this.
#fimo_ranges = function(gf, query) { # prototypical code
# rowRanges(gf) = query
# ans = reduceByRange(gf, MAP=function(r,f) scanTabix(f, param=r))
# ans = unlist(ans, recursive=FALSE) # drop top list structure
# tabs = lapply(ans, lapply, function(x) {
# con = textConnection(x)
# on.exit(close(con))
# dtf = read.delim(con, h=FALSE, stringsAsFactors=FALSE, sep="\t")
# colnames(dtf) = c("chr", "start", "end", "rname", "score", "dir", "pval")
# ans = with(dtf, GRanges(seqnames=chr, IRanges(start, end),
# rname=rname, score=score, dir=dir, pval=pval))
# ans
# })
# GRangesList(unlist(tabs, recursive=FALSE))
#}
rr = fimo_granges(fimo16[, c("POU2F1", "VDR")], myg)
rr## $POU2F1
## $POU2F1$`chr17:38070000-38090000`
## GRanges object with 76 ranges and 4 metadata columns:
## seqnames ranges strand | rname score
## <Rle> <IRanges> <Rle> | <character> <numeric>
## [1] chr17 38070239-38070257 * | chr17:38070239-38070257 -1.5408200
## [2] chr17 38070579-38070597 * | chr17:38070579-38070597 -0.9693880
## [3] chr17 38070851-38070869 * | chr17:38070851-38070869 0.1224490
## [4] chr17 38071025-38071043 * | chr17:38071025-38071043 0.0918367
## [5] chr17 38071253-38071271 * | chr17:38071253-38071271 3.6734700
## ... ... ... ... . ... ...
## [72] chr17 38088602-38088620 * | chr17:38088602-38088620 4.06122
## [73] chr17 38088637-38088655 * | chr17:38088637-38088655 11.69390
## [74] chr17 38089141-38089159 * | chr17:38089141-38089159 13.18370
## [75] chr17 38089439-38089457 * | chr17:38089439-38089457 -1.35714
## [76] chr17 38089822-38089840 * | chr17:38089822-38089840 3.67347
## dir pval
## <character> <numeric>
## [1] + 0.000989
## [2] - 0.000849
## [3] - 0.000631
## [4] - 0.000636
## [5] + 0.000222
## ... ... ...
## [72] + 1.98e-04
## [73] - 1.32e-05
## [74] - 7.09e-06
## [75] - 9.42e-04
## [76] - 2.22e-04
## -------
## seqinfo: 1 sequence from hg19 genome
##
##
## $VDR
## $VDR$`chr17:38070000-38090000`
## GRanges object with 40 ranges and 4 metadata columns:
## seqnames ranges strand | rname score
## <Rle> <IRanges> <Rle> | <character> <numeric>
## [1] chr17 38070016-38070031 * | chr17:38070016-38070031 0.0505051
## [2] chr17 38070387-38070402 * | chr17:38070387-38070402 -3.3838400
## [3] chr17 38070925-38070940 * | chr17:38070925-38070940 5.7171700
## [4] chr17 38071183-38071198 * | chr17:38071183-38071198 -0.6767680
## [5] chr17 38072289-38072304 * | chr17:38072289-38072304 -0.3333330
## ... ... ... ... . ... ...
## [36] chr17 38086915-38086930 * | chr17:38086915-38086930 -0.353535
## [37] chr17 38087304-38087319 * | chr17:38087304-38087319 0.101010
## [38] chr17 38087866-38087881 * | chr17:38087866-38087881 5.343430
## [39] chr17 38088893-38088908 * | chr17:38088893-38088908 -0.111111
## [40] chr17 38089214-38089229 * | chr17:38089214-38089229 1.101010
## dir pval
## <character> <numeric>
## [1] + 3.77e-04
## [2] + 9.66e-04
## [3] - 6.44e-05
## [4] + 4.63e-04
## [5] - 4.21e-04
## ... ... ...
## [36] - 0.000423
## [37] - 0.000371
## [38] + 0.000073
## [39] - 0.000395
## [40] - 0.000277
## -------
## seqinfo: 1 sequence from hg19 genome