ProphAsm

• Introduction
• Cite
• Prerequisities
• Getting started
• Links
• Issues
• Changelog
• Licence
• Author

Introduction

ProphAsm is a tool for computing simplitigs from k-mer sets. Simplitigs are strings obtained as disjoint paths in a bidirectional vertex-centric de Bruijn graph. Compared to unitigs, simplitigs provide an improvement in the number of sequences and their cumulative length, while both representations carry the same k-mers. For more details, see the paper.

Various types of sequencing datasets can be used as the input for ProphAsm, including genomes, pan-genomes, metagenomes or sequencing reads. Besides computing simplitigs, ProphAsm can also compute intersection and set differences of k-mer sets (while set unions are easy to compute simply by merging the source files).

Upon execution, ProphAsm first loads all specified datasets (see the -i param) and the corresponding k-mer sets (see the -k param). If the -x param is provided, ProphAsm then computes their intersection, subtracts the intersection from the individual k-mer sets and computes simplitigs for the intersection. If output files are specified (see the -o param), it computes also set differences.

Cite

To cite the concept of simplitigs and ProphAsm as a tool, please use the following reference:

Břinda K, Baym M, Kucherov G. Simplitigs as an efficient and scalable representation of de Bruijn graphs. Genome Biology 22(96), 2021; doi: https://doi.org/10.1186/s13059-021-02297-z

@article{brinda2021-simplitigs,
  title   = { Simplitigs as an efficient and scalable representation of de {Bruijn} graphs },
  author  = { Karel B{\v r}inda and Michael Baym and Gregory Kucherov },
  journal = { Genome Biology },
  volume  = { 22 },
  number  = { 96 },
  year    = { 2021 },
  doi     = { 10.1186/s13059-021-02297-z }
}

For the concept of simplitigs, you might also consider citing the following paper from another group, introducing independently the same concept under the name spectrum-preserving string sets (SPSS):

Rahman A and Medvedev P. Representation of k-mer sets using spectrum-preserving string sets. Journal of Computational Biology 28(4), pp. 381-394, 2021. https://doi.org/10.1089/cmb.2020.0431

Prerequisities

• GCC 4.8+ or equivalent
• ZLib

Getting started

Download and compile ProphAsm:

git clone https://github.com/prophyle/prophasm
cd prophasm && make -j

Compute simplitigs:

./prophasm -k 15 -i tests/test1.fa -o simplitigs.fa

Set operations:

./prophasm -k 15 -i tests/test1.fa -i tests/test2.fa -o _out1.fa -o _out2.fa -x _intersect.fa -s _stats.tsv

Command line parameters

Program:  prophasm (a greedy assembler for k-mer set compression)
Version:  0.1.1
Contact:  Karel Brinda <kbrinda@hsph.harvard.edu>

Usage:    prophasm [options]

Examples: prophasm -k 15 -i f1.fa -i f2.fa -x fx.fa
             - compute intersection of f1 and f2
          prophasm -k 15 -i f1.fa -i f2.fa -x fx.fa -o g1.fa -o g2.fa
             - compute intersection of f1 and f2, and subtract it from them
          prophasm -k 15 -i f1.fa -o g1.fa
             - re-assemble f1 to g1

Command-line parameters:
 -k INT   K-mer size.
 -i FILE  Input FASTA file (can be used multiple times).
 -o FILE  Output FASTA file (if used, must be used as many times as -i).
 -x FILE  Compute intersection, subtract it, save it.
 -s FILE  Output file with k-mer statistics.
 -S       Silent mode.

Note that '-' can be used for standard input/output.

Algorithm

def extend_simplitig_forward (K, simplitig):
	extending = True
	while extending:
		extending = False
		q = simplitig[-k+1:]
		for x in [‘A’, ‘C’, ‘G’, ‘T’]:
			kmer = q + x
			if kmer in K:
				extending = True
				simplitig = simplitig + x
				K.remove (kmer)
				K.remove (reverse_complement (kmer))
				break
	return K, simplitig

def get_maximal_simplitig (K, initial_kmer):
	simplitig = initial_kmer
	K.remove (initial_kmer)
	K.remove (reverse_complement (initial_kmer))
	K, simplitig = extend_simplitig_forward (K, simplitig)
	simplitig = reverse_complement (simplitig)
	K, simplitig = extend_simplitig_forward (K, simplitig)
	return K, simplitig

def compute_simplitigs (kmers):
	K = set()
	for kmer in kmers:
		K.add (kmer)
		K.add (reverse_complement(kmer))
	simplitigs = set()
	while |K|>0:
		initial_kmer = K.random()
		K, simplitig = get_maximal_simplitig (K, initial_kmer)
		simplitigs.add (simplitig)
	return simplitigs

Links

• Sneak peek at the -tigs! - An overview of different *tigs in computational biology.
• UST - Another tool for computing simplitigs. Unlike ProphAsm, UST requires pre-computed unitigs as the input, therefore the method is overall more resource-demanding.
• BCalm 2 - The best available tool for computing unitigs.
• Unikmer - Another tool for k-mer set operations.

Issues

Please use Github issues.

Changelog

See Releases.

Licence

MIT

Author

Karel Brinda <karel.brinda@hms.harvard.edu>