rs.compute: Computes Similarity of Reactions

In RxnSim: Functions to Compute Chemical and Chemical Reaction Similarity

Computes Similarity of Reactions

Description

Computes similarity between two (or more) input reactions.
rs.compute computes similarity of two reactions.
rs.compute.list computes similarity of two lists of reactions.
rs.compute.sim.matrix computes similarity of reactions in a list.
rs.compute.DB computes similarity of a reaction against a database (parsed from text file).

Usage

rs.compute (rxnA, rxnB, format = 'rsmi', standardize = TRUE, explicitH = FALSE, 
            reversible = TRUE, algo = 'msim', sim.method = 'tanimoto', 
            fp.type = 'extended', fp.mode = 'bit', fp.depth = 6, fp.size = 1024,
            verbose = FALSE, fpCached = FALSE)
rs.compute.list (rxnA, rxnB, format = 'rsmi', standardize = TRUE, explicitH = FALSE,
              reversible = TRUE, algo = 'msim', sim.method = 'tanimoto',
              fp.type = 'extended', fp.mode = 'bit',fp.depth = 6, fp.size = 1024,
              clearCache = TRUE)
rs.compute.sim.matrix (rxnA, format = 'rsmi', standardize = TRUE, explicitH = FALSE,
                    reversible = TRUE, algo = 'msim', sim.method = 'tanimoto', 
                    fp.type = 'extended', fp.mode = 'bit', fp.depth = 6, fp.size = 1024,
                    clearCache = TRUE)
rs.compute.DB (rxnA, DB, format = 'rsmi', ecrange = '*', reversible = TRUE,
              algo = 'msim', sim.method = 'tanimoto', sort = TRUE, fpCached = FALSE)

Arguments

rxnA	input reaction in RSMI format or name (with path) of MDL RXN file. rs.compute.list and rs.compute.sim.matrix accept list of reactions as input.
rxnB	input reaction in RSMI format or name (with path) of MDL RXN file. rs.compute.list accepts list of reactions as input.
DB	parsed database object as returned by rs.makeDB.
format	specifies format of input reaction(s). Reaction(s) can be provided in one of following formats: 'RSMI' (default) or 'RXN'.
ecrange	EC number(s) search pattern while comparing against reaction DB. * is used as wildcard. E.g., 1.2.1.* will restricted search to all reactions with EC numbers starting with 1.2.1.- .
standardize	suppresses all explicit hydrogen if set as TRUE (default).
explicitH	converts all implicit hydrogen to explicit if set as TRUE. It is set as FALSE by default.
reversible	boolean that indicates reversibility of input reaction(s). If set as TRUE (default), reaction(s) are aligned by comparing them in forward direction and by reversing one of them to compute maximum similarity value.
algo	reaction similarity algorithm to be used. One of following algorithms can be used: 'msim' (default), 'msim_max', 'rsim' and 'rsim2'. See description for the details of the algorithms.
sim.method	similarity metric to be used to evaluate reaction similarity. Allowed types include: 'simple', 'jaccard', 'tanimoto' (default), 'russelrao', 'dice', 'rodgerstanimoto', 'achiai', 'cosine', 'kulczynski2', 'mt', 'baroniurbanibuser', 'tversky', 'robust', 'hamann', 'pearson', 'yule', 'mcconnaughey', 'simpson', 'jaccard-count' and 'tanimoto-count'.
fp.type	fingerprint type to use. Allowed types include: 'standard', 'extended' (default), 'graph', 'estate', 'hybridization', 'maccs', 'pubchem', 'kr', 'shortestpath', 'signature' and 'circular'.
fp.mode	fingerprint mode to be used. It can either be set to 'bit' (default) or 'count'.
fp.depth	search depth for fingerprint construction. This argument is ignored for 'pubchem', 'maccs', 'kr' and 'estate' fingerprints.
fp.size	length of the fingerprint bit string. This argument is ignored for the 'pubchem', 'maccs', 'kr', 'estate', 'circular' (count mode) and 'signature' fingerprints.
verbose	boolean that enables display of detailed molecule pairing and reaction alignment (and respective similarity values). The argument is ignored for 'rsim2' algorithm.
sort	boolean than enables rs.compute.DB to return data frame sorted based upon decreasing value of similarities.
fpCached	boolean that enables fingerprint caching. It is set to FALSE by default.
clearCache	boolean that resets the cache before (and after) processing reaction lists. It is set to TRUE by default. Cache can also be explicitly cleared using rs.clearCache.

Details

RxnSim implements four algorithms to compute reaction similarity, namely msim, msim_max, rsim and rsim2.

msim

is based on individual similarities of molecules in two reactions. First, each reactant (product) of a reaction is paired with an equivalent (similar) reactant (product) of the other reaction based on pairwise similarity values using hierarchical grouping. A 0 similarity value is assigned to each unpaired molecule. Reaction similarity is then computed by averaging the similarity values for each pair of equivalent molecule(s) and unpaired molecule(s). Molecule equivalences computed can be reviewed using verbose mode in rs.compute.

msim_max

reaction similarity is computed in the same way as described for msim except that the unpaired molecules are not used for computing average.

rsim

is based on cumulative features of reactant(s) and product(s) of two reactions. Each reaction is represented by two fingerprints, one each for the reactants and another for products. Reaction similarity is computed by averaging similarity values obtained by comparing reactants fingerprint and products fingerprints.

rsim2

is based on cumulative features of all molecules in a reaction forming a reaction fingerprint. Reaction similarity is computed based on the reaction fingerprints of two reactions.

For reversible reactions (reversible = TRUE), apart from comparing reactions in the forward direction they are also compared by reversing one of the reactions. The greater of the two similarity values is reported.

Fingerprint Caching
rs.compute and rs.compute.DB functions can use fingerprint caching. If fpCached is set as TRUE, cache is queried first before generating fingerprints. Any new fingerprint generated is stored in the cache. Setting fpCached = FALSE makes no change to cache. Cache can be cleared by calling rs.clearCache.

rs.compute.list and rs.compute.sim.matrix functions internally use caching. To ensure consistency of fingerprints, rs.clearCache is called internally. Use clearCache = FALSE to override this behaviour; it will use current state of cache and add new fingerprints to it.

Same cache is used for all functions.

Similarity metric included in RxnSim. These metric (except jaccard-count and tanimoto-count) are derived from fingerprint pacakge.

ID	Name	Remarks
simple	Sokal & Michener	bit
jaccard	Jaccard	bit
tanimoto	Tanimoto (bit)	bit and count
jaccard-count	Jaccard (count)	count
tanimoto-count	Tanimoto (count)	count ^
dice	Dice (bit)	bit and count
russelrao	Russel And Rao	bit
rodgerstanimoto	Roger And Tanimoto	bit
achiai	Ochiai	bit
cosine	Cosine	bit
kulczynski2	Kulczynski 2	bit
mt	Modified Tanimoto	bit
baroniurbanibuser	Baroni-Urbani/Buser	bit
robust	Robust (bit)	bit and count
tversky	Tversky*	bit
hamann	Hamann	bit
pearson	Pearson	bit
yule	Yule	bit
mcconnaughey	McConnaughey	bit
simpson	Simpson	bit

*Tversky coefficients can be specified by combining them into a vector, e.g., c('tversky', a, b).

tanimoto (bit), dice (bit) and robust (bit) compute similarity of feature vectors (count mode) by translating them to equivalent fingerprint vectors. Default similarity metric used is tanimoto.

List of fingerprints included in RxnSim. These are derived from rCDK package.

ID	Name of the Fingerprint	Mode
standard	Standard	bit
extended	Extended	bit
estate	EState	bit
graph	Graphonly	bit
hybridization	Hybridization	bit
maccs	MACCS	bit
pubchem	Pubchem	bit
kr	Klekota-Roth	bit
shortestpath	Shortestpath	bit
signature	Signature	count
circular	Circular	bit and count

Value

rs.compute	returns a similarity value.
rs.compute.list	returns a m \times n matrix of similarity values. m and n are the length of two input lists respectively.
rs.compute.sim.matrix	returns a m \times m symmetric matrix of similarity values. m is the length of the input list.
rs.compute.DB	returns a data frame.

Note

While using fingerprint caching (by setting fpCached = TRUE in rs.compute and rs.compute.DB or clearCache = FALSE in rs.compute.list and rs.compute.sim.matrix), ensure that the fingerprints are generated using same parameters values (fp.type, fp.mode, fp.depth and fp.size). To reset cache, call rs.clearCache.

rs.compute.DB uses same parameter values for creating fingerprint as used for (and stored with) DB object (created using rs.makeDB) passed as argument.

Author(s)

Varun Giri [e-mail]

References

^ Carbonell, P., Planson, A-G., Fichera, D., & Faulon J-L. (2011) A retrosynthetic biology approach to metabolic pathway design for therapeutic production. BMC Systems Biology, 5:122.

See Also

rs.makeDB, rs.clearCache, ms.compute

Examples

# Reaction similarity using msim algorithm
rs.compute(rct1, rct2, verbose = TRUE)

RxnSim documentation built on July 26, 2023, 5:41 p.m.