man freecontact (1): fast protein contact predictor

SYNOPSIS

freecontact [OPTION]

freecontact --parprof [evfold|psicov|psicov-sd] < alignment.aln > contacts.out

/usr/share/freecontact/a2m2aln --query '^RASH_HUMAN/(\d+)' < alignment.fa | freecontact --parprof evfold > contacts.out

freecontact --ali=ALIFILE --apply-gapth=BOOL --clustpc=NUM --density=NUM --cov20=BOOL --estimate-ivcov=BOOL --gapth=NUM --icme-timeout=NUM --input-format=[flat|xml] --mincontsep=NUM --output-format=[evfold|pfrmat_rr|bioxsd] --pseudocnt=NUM --pscount-weight=NUM --rho=NUM --threads=NUM --veczw=BOOL

freecontact --help --debug --quiet --version

DESCRIPTION

FreeContact is a protein residue contact predictor optimized for speed. FreeContact can function as an accelerated drop-in for the published contact predictors EVfold-mfDCA of DS. Marks et al. (2011) [1], and PSICOV of D. Jones et al. (2011) [2].

FreeContact is accelerated by a combination of vector instructions, multiple threads, and faster implementation of key parts. Depending on the alignment, 8-fold or higher speedups are possible.

A sufficiently large alignment is required for meaningful results. As a minimum, an alignment with an effective (after-weighting) sequence count bigger than the length of the query sequence should be used. Alignments with tens of thousands of (effective) sequences are considered good input.

jackhmmer(1) or hhblits(1) can be used to generate the alignments, for example.

[1] PLoS One. 2011;6(12):e28766. doi: 10.1371/journal.pone.0028766. Epub 2011 Dec 7. Protein 3D structure computed from evolutionary sequence variation. Marks DS, Colwell LJ, Sheridan R, Hopf TA, Pagnani A, Zecchina R, Sander C.

[2] Bioinformatics. 2012 Jan 15;28(2):184-90. Epub 2011 Nov 17. PSICOV: precise structural contact prediction using sparse inverse covariance estimation on large multiple sequence alignments. Jones DT, Buchan DW, Cozzetto D, Pontil M.

Input

The following formats are supported:

flat

The following simple input file format is used:

 # querystart=5
 # query=QUERYwithinsertionSEQUENCEWITHNOGAPSORINSERTIONS
 QUERYSEQUENCEWITHNOGAPSORINSERTIONS
 -ALIGNED---SEQUENCE--WITH-GAPS-----
 ANOTHER-ALIGNED------------SEQUENCE

The '#' header lines are optional. Header lines are used to calculate contact residue numbers and to look up respective query residues for certain output formats.

If no query is defined, the first sequence in the alignment is used as the query sequence. The query sequence must not contain gaps in the alignment.

All alignment rows must be the same length, and may contain only [ABCDEFGHIJKLMNOPQRSTUVWXYZ-]. [B] is mapped to [D], [Z] is mapped to [E], [JOUX] are mapped to [X]. [X] matches only itself for the entire program.

A2M input alignments can be converted to the above format using /usr/share/freecontact/a2m2aln. a2m2aln can be used to pipe the alignment directly into freecontact.

xml

XML document with one <fc:alignment xmlns:fc=``http://rostlab.org/freecontact/xsd''/> element, defined in the FreeContact schema [4] derived from BioXSD [5].

Example: /usr/share/doc/freecontact/examples/PF00071_v25_1000.xml.

Output

The original EVfold-mfDCA or PSICOV output format is used by default when the respective parameter profile is selected.

evfold (EVfold-mfDCA)

 5 K 6 L 0.332129 3.59798
 | | | | |        + corrected norm (CN) contact score
 | | | | + mutual information (MI) score
 | | | + contact amino acid residue code
 | | + contact residue number
 | + contact amino acid residue code
 + contact residue number

Contacts are sorted on residue number.

pfrmat_rr (PSICOV)

CASP residue-residue separation prediction (PFRMAT RR) format [3]:

 55 67 0 8 10.840280
 |  |  | | + contact score
 |  |  +-+ range [Å] of Cb-Cb distance predicted for the residue pair
 |  |      (C-alpha for glycines)
 |  |      These two fields are invariant in the output.
 |  + contact residue number
 + contact residue number

Contacts are sorted on score, descending.

[3] <http://predictioncenter.org/casp10/index.cgi?page=format>

bioxsd

XML document with one <fc:contactMap xmlns:fc=``http://rostlab.org/freecontact/xsd''/> element, defined in the FreeContact schema [4] derived from BioXSD [5].

Example: /usr/share/doc/freecontact/examples/PF00071_v25_1000.evfold.50.xml.

Note: as BioXSD is under active development in collaboration with FreeContact, the FreeContact schema may actually be derived from a version not yet available at [5].

[4] <file:///usr/share/freecontact/freecontact.xsd>

[5] <http://bioxsd.org>

The output may not list all possible contacts.

REFERENCES

: Submitted. FreeContact: fast and free direct residue-residue contact prediction. Kaján L, Sustik MA, Marks DS, Hopf TA, Kalaš M, Rost B.

OPTIONS

-a [ --threads ] arg

Threads to use [0-). 0 means as many as cores.

--apply-gapth arg

When true, exclude residue columns and rows with a weighted gap frequency > --gapth from the covariance matrix [Boolean].

-c [ --clustpc ] arg

BLOSUM clustering percentage [0-100].

--cov20 arg

If true, leave one amino acid off the covariance matrix, making it non-overdetermined [Boolean].

-d [ --density ] arg

Target precision matrix density [0-1]. Set 0 to not control density.

--debug

Turn on debugging.

--estimate-ivcov arg

Use inverse covariance matrix estimation instead of matrix inversion [Boolean].

-f [ --ali ] arg (=-)

Alignment file [path]. If '-', standard input. Default: '-'.

-g [ --gapth ] arg

Weighted gap frequency threshold (0-1].

-h [ --help ]

Produce this help message.

-i [ --input-format ] arg (=flat)

Input format [flat|xml].

--icme-timeout arg (=1800)

Inverse covariance matrix estimation timeout in seconds [0-). Applied to each iversion call independently. If a timeout occurs, the program exits with status 2.

--mincontsep arg

Minimum sequence-wise contacting residue pair separation given in amino acids as (j-i>=arg). 1 for adjacent residues. [1-).

-o [ --output-format ] arg

Output format [evfold|pfrmat_rr|bioxsd].

--parprof arg (=default)

Parameter profile (optional) [default|evfold|psicov]. The default profile is evfold.

Command line arguments can be used to override profile values.

evfold: Triggers EVfold-mfDCA [1] compatibility mode.
psicov: Triggers PSICOV [2] compatibility mode.
psicov-sd: Triggers PSICOV [2] sensible default mode: fixed default rho, no density control.

-w [ --pscount-weight ] arg

Pseudocount weight [0-1].

-p [ --pseudocnt ] arg

Pseudocount [0-).

--pep

Print effective parameters on standard error. Use this option to see what parameters freecontact(1) is run with in detail. This is especially useful when the --parprof option is used in combination with other options.

--rho arg

Initial value of Glasso regularization parameter [0-). If negative, choose value automatically.

--quiet arg (=0)

Print nothing but error messages on standard error. Does not affect --debug.

--veczw arg

Use vectorized sequence weighting when available [Boolean].

--version

Print version.

EXIT STATUS

0: No error - success.
1: Unspecified error.
2: A timeout (see --icme-timeout) occurred.

EXAMPLES

 /usr/share/freecontact/a2m2aln --query '^RASH_HUMAN/(\d+)' < '/usr/share/doc/freecontact/examples/PF00071_v25_1000.fa' | \
  freecontact --parprof evfold > PF00071_v25_1000.evfold
 freecontact --parprof evfold -i xml -o bioxsd < '/usr/share/doc/freecontact/examples/PF00071_v25_1000.xml' > PF00071_v25_1000.evfold.xml
 freecontact --parprof psicov < /usr/share/doc/freecontact/examples/demo_1000.aln > demo_1000.psicov

NOTES

For optimal performance, use the Automatically Tuned Linear Algebra Software (ATLAS) library compiled on the machine where freecontact is run.

AUTHOR

László Kaján <[email protected]>