Table 6.

Sankoff-type (base-pair probabilities) RSP tools based on comparative sequence analysis

Characteristic		Sankoff-type (Base-pair) Probabilities) RSP Tool		Description	Input	Output	Applicable Species	Active (T)/Inactive (F)
Conservation	Suboptimal Prediction	Local interaction length	PMcomp [186]	A method to compute pairwise and progressive multiple alignments from the direct comparison of base pairing probability matrices, including structural alignment	Two RNA sequences	Computation of base pairing probability matrices via McCaskill’s approach Extraction of the maximum-weight common secondary structure and an associated alignment via a simplified variant of Sankoff's algorithms	Bacteria, human, virus	F
		Global Interaction Length	FoldalignM (dependent on Vienna RNA package) (ncRNA) [188]	A multiple RNA structural alignment method, to a large extent based on the PMcomp program	Two or more RNA sequences or entire sequences and allow MSA as input	Capable of structural alignments for ncRNA Discovery of new ncRNAs Identification of the structure of novel ncRNAs Alignments improvement for known ncRNAs	Bacteria, human, virus	T
			Murlet [189]	A practical multiple alignment tool for structural RNA sequences. It implements an efficient scoring system that reduces the time and space requirements considerably without compromizing on the alignment quality	RNA sequences in FASTA format with a maximum length of 300 nt	Computation of the match probability matrix (align-ability of each position pair between sequences and the base pairing probability matrix) Scoring of RNA alignment using the Sankoff algorithm Prediction of the consensus secondary structure of the alignment via external programs Better accuracy in alignment and structure prediction than ClustalW, Stemloc and RNAcast	Eukaryote	T
	No Suboptimal		LocARNA (local alignment of RNA)/LocARNA -P [187, 252]	A fast and accurate comparison of RNAs with respect to their sequence and structure	RNA sequences in FASTA format (recommendation for the analysis of RNAs ≤60% sequence identity, where alignments based on only sequence similarity are unreliable)	Generation of a multiple alignment together with a consensus structure Extraction of putative RNA classes from genome-wide surveys for structured RNAs Robust against false positive predictions (e.g., contamination of the input data with unstructured or non-conserved sequences) LocARNA: folding via RNAfold or mfold; alignment via RIBOSUM-like similarity scoring and realistic gap cost LocARNA -P is more accurate boundary prediction and improved detection of structural RNAs than LocARNA	Virus, bacteria, plant	T
		Local interaction length	StrAl with PETcofold (ncRNA) [190]	A progressive alignment of ncRNA using base pairing probability vectors in quadratic time, where a scoring function is available for sequence similarity as well as up- and downstream pairing probability	A set of alignments with several sequences per alignment	Alignment of ncRNA based on a heuristic method with reduced sequence-structure alignment to a two-dimensional problem similar to standard MSA	Viruses, bacteria, eukaryote	F

MSA: multiple sequence alignment; ncRNA: noncoding RNA; nt: number of nucleotides; RNA: ribonucleic acid; RSP: RNA structural prediction