Lutefisk - de novo MS/MS Sequencing

lu·te·fisk \´lüd·e¸fisk, ´ lüe-\ or lut·fisk \´lüt¸f-\ also lu-
de·fisk \´lüde-\ or lud·fisk \´ lüd¸f-\ n -s [lutefisk fr. Norw,
fr. lute to wash in lye solution + fisk fish; lutfisk fr. Sw, fr.
luta to wash in lye solution + fisk fish; ludefisk & ludfisk fr.
Dan ludfisk fr. lude to wash in lye solution + fisk fish; Norw
lute, Sw luta, Dan lude akin to ON laug bath, hot spring; Norw
& Sw & Dan fisk fr. ON fiskr fish -- more at LYE, FISH]
: stockfish that has been soaked in lye water, skinned, boned,
and boiled

Lutefisk is software for the de novo interpretation of peptide CID spectra

High quality tandem mass spectra of peptides are often obtained for which no exact database match can be made. Consequently, we are faced with the question of whether the protein under investigation is novel, or if the non-matching spectra are due to less exciting prospects such as inter-species variation, database sequence errors, or unexpected proteolytic cleavages. To begin addressing this problem we perform a de novointerpretation of the CID spectra using the computer program Lutefisk; however, any such interpretations nearly always yield multiple sequence candidates, where it is often difficult or impossible to distinguish the correct sequence from the incorrect ones. The variations between candidate sequences are often minor and typically involve dipeptide inversions, swapping of dipeptides of the same mass, replacements of dipeptides with single amino acids of the same mass, and replacements of amino acids by dipeptides of the same mass. We use the multiple sequence candidates produced by Lutefisk as query sequences in a second program, CIDentify. CIDentify is a version of Bill Pearson's FASTA algorithm modified by Alex Taylor to accommodate MS nuances such as multiple query sequences, ambiguous dipeptides and isobaric mass equivalencies.

Download:

Lutefisk has now been released under the GNU General Public License (GPL). ANSI C Source code which can be compiled for MacOS X, Windoze, Linux, Solaris, Irix, AIX, or OSF and a Windoze binary can be downloaded from sourceforge.

Source code and executables for CIDentify can be obtained from the CIDentify folder at the FASTA site at the University of Virginia.

User's Guide:

LutefiskXP Manual

References:

R. S. Johnson and J. A. Taylor (2002) "Searching sequence databases via de novo peptide sequencing by tandem mass spectrometry", Mol. Biotechnology Vol. 22, No. 3. (November 2002), pp. 301-315.

J. A. Taylor and R. S. Johnson (2000) "Implementation and uses of automated de novo peptide sequencing by tandem mass spectrometry". Anal. Chem. 73:2594-2604. [PDF (login required)]

R. S. Johnson and J. A. Taylor (2000) "Searching sequence databases via de novo peptide sequencing by tandem mass spectrometry", "Protein and Peptide Analysis: Advances in the Use of Mass Spectrometry", 146:41-61 (Methods in Molecular Biology series, Humana Press).

J. A. Taylor and R. S. Johnson (1997) "Sequence database searches via de novo peptide sequencing by tandem mass spectrometry". Rapid Comm. Mass Spec.. 11:1067-1075. [PDF (account required)]

How Does It Work?:

This is a general flowchart depicting the major portions of the algorithm:

illustrated example

License / Contact Info:

Lutefisk has now been released under the GNU General Public License (GPL).

This program is free software; you can redistribute it and/or

modify it under the terms of the GNU General Public License

as published by the Free Software Foundation; either version 2

of the License, or (at your option) any later version.
 

This program is distributed in the hope that it will be useful,

but WITHOUT ANY WARRANTY; without even the implied warranty of

MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the

GNU General Public License for more details.

 
You should have received a copy of the GNU General Public License

along with this program; if not, write to the Free Software

Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA  02110-1301, USA.