IntEREst: Intron-Exon Retention Estimator

matchPwmToReference<-function(pwm, pwmSsIndex=11, referenceChr, referencePos, 
	referenceIntronExon, intronExon="intron", matchWindowRelativePos=c(NA,NA), 
	minMatchScore="80%", refGenome=""){

	# Check if reference genome sequence is of BSgenome type
	if (is(refGenome, "BSgenome")){

		# Check if only intron sequences should be checked for U12 annotation 
		if(length(intronExon)==1){
			# Check whether an upstream or downstream window is NOT defined for 
			#the PWM matching
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){
				seqIntEx=Biostrings::getSeq(refGenome, 
					names=referenceChr[referenceIntronExon==intronExon], 
					start=(referencePos+(matchWindowRelativePos[1]))[
						referenceIntronExon==intronExon], 
					end=(referencePos+matchWindowRelativePos[2])[
						referenceIntronExon==intronExon],
					as.character=TRUE)
			# Check whether an upstream or downstream window is defined for the 
			#PWM matching
			} else {
				seqIntEx=Biostrings::getSeq(refGenome, 
					names=referenceChr[referenceIntronExon==intronExon], 
					start=(referencePos-(pwmSsIndex-1))[
						referenceIntronExon==intronExon], 
					end=(referencePos+(ncol(pwm)-pwmSsIndex))[
						referenceIntronExon==intronExon],
					as.character=TRUE)
			}
		# Check if all (intron and exon) sequences should be checked for 
		#U12 annotation  
		} else if ( length(which(intronExon=="intron"))==1 & 
			length(which(intronExon=="exon"))==1 ) {
			
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){
				# run if upstream or downstream windows are NOT defined for the 
				#PWM matching
				seqIntEx=Biostrings::getSeq(refGenome, 
					names=referenceChr[referenceIntronExon==intronExon[1] | 
						referenceIntronExon==intronExon[2]], 
					start=(referencePos+(matchWindowRelativePos[1]))[
						referenceIntronExon==intronExon[1] |
							referenceIntronExon==intronExon[2]], 
					end=(referencePos+matchWindowRelativePos[2])[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]],
					as.character=TRUE)
			} else {
				# run if upstream or downstream windows are defined for the 
				#PWM matching
				seqIntEx=Biostrings::getSeq(refGenome, 
					names=referenceChr[referenceIntronExon==intronExon[1] | 
						referenceIntronExon==intronExon[2]], 
					start=(referencePos-(pwmSsIndex-1))[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]], 
					end=(referencePos+(ncol(pwm)-pwmSsIndex))[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]],
					as.character=TRUE)
			}


		} else {
			msg<- 
"Invalid intronExon parameter. Check ?matchPwmToReference for more 
information."
			stop(msg)
		}

		matchInd= lapply(seqIntEx, function(tmp) { 
			test=Biostrings::matchPWM(pwm, tmp, min.score=minMatchScore,
				with.score=TRUE)
			return( list(len=length(GenomicRanges::ranges(test)), 
				score=max(S4Vectors::mcols(test)$score)) )
			})

		lenMatchInd<- 
			as.vector(unlist(sapply(matchInd, function(tmp) return(tmp$len))))
		matchScore<- rep(0,length(lenMatchInd))
		matchScoreTmp<-as.vector(unlist(sapply(matchInd, function(tmp) 
			return(tmp$score))))
		validInd<- which(!is.na(matchScoreTmp)& !is.infinite(matchScoreTmp) & 
					!is.null(matchScoreTmp))
		if(length(which(lenMatchInd>0))>0)
			matchScore[which(lenMatchInd>0)]<- matchScoreTmp[validInd]


	} else if (is(refGenome, "DNAStringSet")){

		# Check if only intron sequences should be checked for U12 annotation 
		if(length(intronExon)==1){
			# Check whether an upstream or downstream window is NOT defined for 
			#the PWM matching
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){
				tmpGr<- GenomicRanges::GRanges (
					referenceChr[referenceIntronExon==intronExon], 
					IRanges((referencePos+(matchWindowRelativePos[1]))[
						referenceIntronExon==intronExon],
						(referencePos+matchWindowRelativePos[2])[
						referenceIntronExon==intronExon]))

				seqIntEx=as.character(Biostrings::getSeq(refGenome, 
					tmpGr))
			# Check whether an upstream or downstream window is defined for the 
			#PWM matching
			} else {
				tmpGr<- GenomicRanges::GRanges (
					referenceChr[referenceIntronExon==intronExon], 
					IRanges(
						(referencePos-(pwmSsIndex-1))[
							referenceIntronExon==intronExon],
						(referencePos+(ncol(pwm)-pwmSsIndex))[
							referenceIntronExon==intronExon]))

				seqIntEx=as.character(Biostrings::getSeq(refGenome, 
					tmpGr))
			}
		# Check if all (intron and exon) sequences should be checked for 
		#U12 annotation  
		} else if ( length(which(intronExon=="intron"))==1 & 
			length(which(intronExon=="exon"))==1 ) {
			
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){
				# run if upstream or downstream windows are NOT defined for the 
				#PWM matching
				tmpGr<-  GenomicRanges::GRanges (
					referenceChr[referenceIntronExon==intronExon[1] | 
						referenceIntronExon==intronExon[2]], 
					IRanges(
						(referencePos+(matchWindowRelativePos[1]))[
						referenceIntronExon==intronExon[1] |
							referenceIntronExon==intronExon[2]],
						(referencePos+matchWindowRelativePos[2])[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]]))

				seqIntEx=as.character(Biostrings::getSeq(refGenome, 
					tmpGr))
			} else {
				# run if upstream or downstream windows are defined for the 
				#PWM matching
				tmpGr<-  GenomicRanges::GRanges (
					referenceChr[referenceIntronExon==intronExon[1] | 
						referenceIntronExon==intronExon[2]], 
					IRanges(
						(referencePos-(pwmSsIndex-1))[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]],
						(referencePos+(ncol(pwm)-pwmSsIndex))[
						referenceIntronExon==intronExon[1] | 
							referenceIntronExon==intronExon[2]]))


				seqIntEx=as.character(Biostrings::getSeq(refGenome, 
					tmpGr))
			}


		} else {
			msg<- 
"Invalid intronExon parameter. Check ?matchPwmToReference for more 
information."
			stop(msg)
		}

		matchInd= lapply(seqIntEx, function(tmp) { 
			test=Biostrings::matchPWM(pwm, tmp, min.score=minMatchScore,
				with.score=TRUE)
			return( list(len=length(GenomicRanges::ranges(test)), 
				score=S4Vectors::mcols(test)$score) )
			}) 

		lenMatchInd<- 
			as.vector(unlist(sapply(matchInd, function(tmp) return(tmp$len))))
		matchScore<- rep(0,length(lenMatchInd))
		matchScoreTmp<-as.vector(unlist(sapply(matchInd, function(tmp) 
			return(tmp$score))))
		validInd<- which(!is.na(matchScoreTmp)& !is.infinite(matchScoreTmp) & 
					!is.null(matchScoreTmp))
		if(length(which(lenMatchInd>0))>0)
			matchScore[which(lenMatchInd>0)]<- matchScoreTmp[validInd]


	} else if (file.exists(refGenome)) {
		#Run if reference genome sequence is a fasta file
		fa=seqinr::read.fasta(file = refGenome)
		# Check if only intron sequences should be checked for U12 annotation
		if(length(intronExon)==1){
			# Check whether an upstream or downstream window is NOT defined for
			#the PWM matching
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){

				seqIntEx=unlist(lapply( which(referenceIntronExon==intronExon),
					function(temp) seqinr::getSequence(seqinr::getFrag(
						object=fa[as.character(referenceChr)[temp]],
						begin=(referencePos+(matchWindowRelativePos[1]))[temp],
						end=(referencePos+matchWindowRelativePos[2])[temp]), 
							as.string=TRUE)))
			
			# Check whether an upstream or downstream window is defined for the
			#PWM matching
			} else {

				seqIntEx=unlist(lapply( which(referenceIntronExon==intronExon), 
					function(temp) seqinr::getSequence(seqinr::getFrag(
						object=fa[as.character(referenceChr)[temp]], 
						begin=(referencePos-(pwmSsIndex-1))[temp], 
						end=(referencePos+(ncol(pwm)-pwmSsIndex))[temp]), 
							as.string=TRUE)))

			}
		# Check if all (intron and exon) sequences should be checked for U12
		#annotation
		} else if ( length(which(intronExon=="intron"))==1 & 
			length(which(intronExon=="exon"))==1 ) {
			# Check Whether an upstream or downstream window is NOT defined for
			#the PWM matching
			if((!is.na(matchWindowRelativePos[1])) & 
				(!is.na(matchWindowRelativePos[2]))){

				seqIntEx=unlist(lapply( which(
					referenceIntronExon==intronExon[1]| 
						referenceIntronExon==intronExon[2]), 
					function(temp) seqinr::getSequence(seqinr::getFrag(
						object=fa[as.character(referenceChr)[temp]], 
						begin=(referencePos+(matchWindowRelativePos[1]))[temp],
						end=(referencePos+matchWindowRelativePos[2])[temp]),
							as.string=TRUE)))

			# Check whether an upstream or downstream window is defined for the
			#PWM matching
			} else {

				seqIntEx=unlist(lapply( which(
					referenceIntronExon==intronExon[1]| 
						referenceIntronExon==intronExon[2]), 
					function(temp) seqinr::getSequence(seqinr::getFrag(
						object=fa[as.character(referenceChr)[temp]], 
						begin=(referencePos-(pwmSsIndex-1))[temp], 
						end=(referencePos+(ncol(pwm)-pwmSsIndex))[temp]), 
							as.string=TRUE)))

			}
		} else {
			msg<-
"Invalid intronExon parameter. Check ?matchPwmToReference for more 
information."
			stop(msg)
		}

		matchInd= lapply(seqIntEx, function(tmp) { 
			test=Biostrings::matchPWM(pwm, tmp, min.score=minMatchScore, 
				with.score=TRUE)
			return( list(len=length(GenomicRanges::ranges(test)), 
				score=S4Vectors::mcols(test)$score) )
			}) 

		lenMatchInd<- 
			as.vector(unlist(sapply(matchInd, function(tmp) return(tmp$len))))
		matchScore<- rep(0,length(lenMatchInd))
		matchScoreTmp<-as.vector(unlist(sapply(matchInd, function(tmp) 
			return(tmp$score))))
		validInd<- which(!is.na(matchScoreTmp)& !is.infinite(matchScoreTmp) & 
					!is.null(matchScoreTmp))
		if(length(which(lenMatchInd>0))>0)
			matchScore[which(lenMatchInd>0)]<- matchScoreTmp[validInd]



	}


	pwmMatchBool=lenMatchInd>0

	res=data.frame(pwmMatchBool=pwmMatchBool, pwmMatchScore=matchScore)
	return(res)

}