ProfileSegments makes optimal alignments showing the segments of similarity found by ProfileSearch.
See the Profile Analysis Essay for an introduction to associating distantly related proteins and finding structural motifs.
ProfileSearch and ProfileSegments use the method of Gribskov, et al (Proc. Natl. Acad. Sci. USA 84; 4355-4358 (1987)). ProfileSearch compares a profile to a set of sequences and lists the sequences that contain a region similar to the profile. ProfileSegments is used to display an optimized alignment between the best segment of similarity in each sequence in the list and the profile. ProfileSegments uses the alignment procedure of Smith and Waterman (Advances in Applied Mathematics 2; 482-489 (1981)) to search for and align the segments. The scoring matrix values, gap creation penalties, and gap extension penalties used to find the best region of similarity between the profile and the sequence are all present in the input file itself and need not be set.
Here is some of the output file:
(Local) PROFILESEGMENTS of: JC4853 check: 4250 from: 1 to: 646
P1;JC4853 - dnaK-type molecular chaperone hsc73 - mouse
N;Alternate names: heat-shock protein 73
C;Species: Mus musculus (house mouse)
C;Date: 15-Aug-1996 #sequence_revision 18-Oct-1996 #text_change 13-Mar-1998
C;Accession: JC4853
R;Soulier, S.; Vilotte, J.L.; L'Huillier, P.J.; Mercier, J.C. . . .
to: hsp70.prf check: 1246 from: 1 to: 743
(Peptide) PROFILEMAKE v4.50 of: hsp70.msf{*} Length: 743
Sequences: 25 MaxScore: 2168.13 October 7, 1998 17:48
Gap: 1.00 Len: 1.00
GapRatio: 0.33 LenRatio: 0.10
hsp70.msf{S11448} From: 1 To: 743 Weight: 1.00
hsp70.msf{S06443} From: 1 To: 743 Weight: 1.00 . . .
Profile: hsp70.prf
Gap Weight: 24.000 Average Match: 1.094
Length Weight: 0.270 Average Mismatch: -0.993
Quality: 1726.80 Length: 693
Ratio: 2.67 Gaps: 17
jc4853 x hsp70.prf October 21, 1998 16:51 ..
. . . . .
S 1 MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT.DTER 49
. |:||||||||||||::::..|||||||||||||||||||| |:||
P 27 MTKGPAIGIBLGTTYSCVGVWQHGRVEIIANBQGNRTTPSYVAFTQBTER 76
//////////////////////////////////////////////////////////////
(Local) PROFILESEGMENTS of: S07197 check: 4250 from: 1 to: 646
P1;S07197 - dnaK-type molecular chaperone hsc73 - rat
N;Alternate names: heat shock cognate protein hsc70; heat shock cognate protein
hsc73
C;Species: Rattus norvegicus (Norway rat)
C;Date: 29-Jan-1993 #sequence_revision 29-Jan-1993 #text_change 30-Jan-1998
C;Accession: S07197; I57594; S35606
R;Sorger, P.K.; Pelham, H.R.B. . . .
to: hsp70.prf check: 1246 from: 1 to: 743
(Peptide) PROFILEMAKE v4.50 of: hsp70.msf{*} Length: 743
Sequences: 25 MaxScore: 2168.13 October 7, 1998 17:48
Gap: 1.00 Len: 1.00
GapRatio: 0.33 LenRatio: 0.10
hsp70.msf{S11448} From: 1 To: 743 Weight: 1.00
hsp70.msf{S06443} From: 1 To: 743 Weight: 1.00 . . .
Profile: hsp70.prf
Gap Weight: 24.000 Average Match: 1.094
Length Weight: 0.270 Average Mismatch: -0.993
Quality: 1726.80 Length: 693
Ratio: 2.67 Gaps: 17
s07197 x hsp70.prf October 21, 1998 16:51 ..
. . . . .
S 1 MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT.DTER 49
. |:||||||||||||::::..|||||||||||||||||||| |:||
P 27 MTKGPAIGIBLGTTYSCVGVWQHGRVEIIANBQGNRTTPSYVAFTQBTER 76
. . . . .
//////////////////////////////////////////////////////////////
ProfileSegments reads the ProfileSearch output file in order to obtain the names of the sequences, the name of the profile, and the gap creation and gap extension penalties. You can tell ProfileSegments to ignore any of the sequence files in the list by editing this file. To do this, insert an exclamation point (!) as the first character of the line that you wish to comment out. If the profile that was used in ProfileSearch cannot be identified and read correctly from the information in the text heading of the input file, ProfileSegments complains and stops.
If the gap creation penalty and gap extension penalty cannot be read correctly from the information in the text heading of the input file, ProfileSegments calculates values from the profile itself, using the maximum match value that is present in the profile: 3 x MaxMatch for the gap creation penalty and MaxMatch / 30 for the gap extension penalty.
PileUp creates a multiple sequence alignment from a group of related sequences. LineUp is a multiple sequence editor used to create multiple sequence alignments. Pretty displays multiple sequence alignments.
ProfileMake makes a profile from a multiple sequence alignment. ProfileSearch uses the profile to search a database for sequences with similarity to the group of aligned sequences. ProfileSegments displays optimal alignments between each sequence in the ProfileSearch output list and the group of aligned sequences (represented by the profile consensus). ProfileGap makes optimal alignments between one or more sequences and a group of aligned sequences represented as a profile. ProfileScan finds structural and sequence motifs in protein sequences, using predetermined parameters to determine significance.
We have little experience using nucleotide sequences with profile analysis.
The surface of comparison (see BestFit) may not be more than some value set within the program (5.5 million at most institutions). Profiles may not be longer than 1,000 residues or bases. Sequences that are too long for the surface of comparison are divided into smaller segments that are aligned separately (see the CONSIDERATIONS topic, below).
See the Profile Analysis Essay for an introduction to associating distantly related proteins and finding structural motifs.
ProfileSegments reads the profile, the profile's consensus sequence, and the set of sequences in the list created by ProfileSearch and then uses the same algorithm as BestFit to align each sequence to the profile. The alignment is made with the values in the profile. The display is made with the consensus sequence and values from the profile. For a detailed description of Smith and Waterman-style alignments, see the BestFit program's entry.
There is strong reason to believe that the BestFit algorithm used by ProfileSegments is the best known way to find segments of similarity, but the best parameters must be determined empirically. Like any alignment program, ProfileSegments produces alignments that are very different depending on the scoring matrix values and gap coefficients used to make up the profile, and the gap penalties used as input to ProfileSearch.
Unless you use -LIMit, sequences that are too long for the surface of comparison are always divided into smaller, overlapping segments that are aligned separately. -LIMit may permit long sequences to be aligned without division. Sequences longer than 32,000 are always divided and aligned as separate segments. Although ProfileGap and ProfileSegments overlap the points of division by the whole length of the profile, divided sequences may not align properly if the segment of similarity crosses the point where the sequence was divided.
-GLObal makes ProfileGap and ProfileSegments display the alignment of the whole sequence to the whole profile, instead of just the most-similar segment between the sequence and the profile. This is analogous to executing a Gap between the profile and sequence.
ProfileSearch/ProfileSegments finds only the best fit of the profile to any sequence. Be aware that other regions with a lower degree of similarity to the profile may also exist in the same sequence, especially in nucleic acid sequences.
You can set the parameters listed below from the command line. For more information, see "Using Program Parameters" in Chapter 3, Using Programs in the User's Guide.