# PfTools   v3.2

(C) Copyright SIB Swiss Institute of Bioinformatics
available from  https://github.com/sib-swiss/pftools3 under GPL v2. See LICENSE.


Version 3 contains the original FORTRAN 77 pftools (release 2.3)
and the new pftoolsV3 programs.

The 'pftools' package documententation is unfortunately scattered over many
different places. Here is an annotated list of the relevant documents we are
aware of:

# Generalized profile syntax

A description of the generalized profile syntax is given in file:

- [doc/profile.txt](https://raw.githubusercontent.com/sib-swiss/pftools3/master/doc/profile.txt)  (original document)
- [doc/profile.pdf](https://raw.githubusercontent.com/sib-swiss/pftools3/master/doc/profile.pdf)  (revised and completed version)

it was originally published in

* Bucher P, Bairoch A.
  A generalized profile syntax for biomolecular sequence motifs
  and its function in automatic sequence interpretation.
  Proc Int Conf Intell Syst Mol Biol. 1994;2:53-61.
  PubMed PMID: [7584418](https://www.ncbi.nlm.nih.gov/pubmed/7584418) .


# Command-line tutorial

In the doc/example subdirectory, the [test_V3.sh](https://raw.githubusercontent.com/sib-swiss/pftools3/master/doc/example/test_V3.sh) shell script is a good starting
point for using pfsearchV3/pfscanV3

# Algorithms description

Technical details about how profiles can be constructed and parametrized
are summarized in file:

- [doc/profile.pdf](https://raw.githubusercontent.com/sib-swiss/pftools3/master/doc/profile.pdf)

The very first paper describing the PFTOOLS algorithms is

* Lüthy R, Xenarios I, Bucher P.
  Improving the sensitivity of the sequence profile method.
  Protein Sci. 1994 Jan;3(1):139-46.
  PubMed PMID: [7511453](https://www.ncbi.nlm.nih.gov/pubmed/7511453); PubMed Central PMCID: PMC2142471.

The generalized profile alignment method is closely related to other "classical"
algorithm for aligning sequences. For example, it encompasses the Smith-Waterman
algorithm and the Viterbi decoding of profile-HMM (as implemented in HMMER2 for
example). Relationships between these algorithm were investigated in

* Bucher P, Hofmann K.
  A sequence similarity search algorithm based on a probabilistic interpretation of an alignment scoring system.
  Proc Int Conf Intell Syst Mol Biol. 1996;4:44-51. Review.
  PubMed PMID: [8877503](https://www.ncbi.nlm.nih.gov/pubmed/8877503).

* Bucher P, Karplus K, Moeri N, Hofmann K.
  A flexible motif search technique based on generalized profiles.
  Comput Chem. 1996 Mar;20(1):3-23.
  PubMed PMID: [8867839](https://www.ncbi.nlm.nih.gov/pubmed/8867839).

Relatively detailed explanations about the profile normalized scores, as well as its
comparisons with other popular statistics for sequence alignments can be found in

* Pagni M, Jongeneel CV.
  Making sense of score statistics for sequence alignments.
  Brief Bioinform. 2001 Mar;2(1):51-67.
  PubMed PMID: [11465063](https://www.ncbi.nlm.nih.gov/pubmed/11465053).

The heuristic score is succinctly described in

* Schuepbach T, Pagni M, Bridge A, Bougueleret L, Xenarios I, Cerutti L.
  pfsearchV3: a code acceleration and heuristic to search PROSITE profiles.
  Bioinformatics. 2013 May 1;29(9):1215-7. doi: 10.1093/bioinformatics/btt129.
  PubMed PMID: [23505298](https://www.ncbi.nlm.nih.gov/pubmed/23505298); PubMed Central PMCID: PMC3634184.

# Applications of the Pftools

Two databases were created based on the PFTOOLS technology: PROSITE and HAMAP
and they are still actively maintained

1. https://prosite.expasy.org/
1. https://hamap.expasy.org/

The PFTOOLS were initially designed with handling capabilities of DNA sequences.
The latest released pfsearchV3 feature support for FASTQ and SAM formats. DNA
applications are for example given in

* Pagni M, Niculita-Hirzel H, Pellissier L, Dubuis A, Xenarios I, Guisan A, Sanders IR, Goudet J, Guex N.
  Density-based hierarchical clustering of pyro-sequences on a large scale - the case of fungal ITS1.
  Bioinformatics. 2013 May 15;29(10):1268-74. doi: 10.1093/bioinformatics/btt149.
  PubMed PMID: [23539304](https://www.ncbi.nlm.nih.gov/pubmed/23539304) ; PubMed Central PMCID: PMC3654712.

* Schmid-Siegert E, Richard S, Luraschi A, Mühlethaler K, Pagni M, Hauser PM.
  Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii.
  MBio. 2017 Nov 7;8(6). pii: e01470-17. doi: 10.1128/mBio.01470-17.
  PubMed PMID: [29114024](https://www.ncbi.nlm.nih.gov/pubmed/29114024); PubMed Central PMCID: PMC5676039.

# Authors

Mas:
- Philipp Bucher developped the Fortran code
- Thierry Schuepbach developped the C code

Other contributors:
- Kay Hofmann
- Volker Flegel
- Edouard de Castro
- Lorenzo Cerruti
- Marco Pagni
- Sébastien Moretti
- Jerven Tjalling Bolleman

[SIB Swiss Institute of Bioinformatics](https://www.sib.swiss/)
[Vital-IT Group](https://www.vital-it.ch/)
Quartier Sorge - Batiment Amphipole
1015 Lausanne
Switzerland

