---

Code for Semantic Similarity Measures

This software returns semantics similarity scores for a given gene list based on GO ontology files, and GO Annotations files. There are 6 methods available in this code: Resnik, Jiang, Lin, ISM_Resnik, ISM_Jiang, and ISM_Lin, where ISM is the proposed method in the paper:

H. Yang, T. Nepusz, and A. Paccanaro, Improving GO semantic similarity measures by exploring the ontology beneath the terms and modelling uncertainty Bioinformatics, vol. 28, iss. 10, pp. 1383-1389, 2012.

The authors give permission for use, modification, and distribution of this software for any purpose.

In the default setting, the software uses the pre-downloaded GO ontology file, and the GO Annotations file. However, it provides an option of automatically downloading the recent GO ontology file. This software also allows the users to choose organisms, semantic similarity measures, and evidence codes ignored.

There are four main functions in this software:  DOALL, INITIALIZE, GoSim, and GeneSim:

• INITIALIZE -- for a given, tree, it does all the steps necessary for semantic similarity calculation: parse the go ontology file, parse the go annotation file, get the number of genes annotated to a term, find the minimum number of annotations appearing in the least common ancester of two terms, and pre-compute all term similarities.
• DOALL -- it does all these things as INITIALIZE for three trees; moreover, it pre-computes gene product similarities.
• GoSim -- it returns the GO term similarity for the GoList.
• GeneSim -- it returns the gene product similarity for the GeneList

For a starter who wants only basic usage, see the examples below; for an advanced user, go to here to check the usage of these functions.

As this distribution contains some downloaded annotation files, and a downloaded GO ontology files, we acknowledge the Gene Ontology Consortium as the source of this software.

Download

We provide five sets of files for you to download:

• F1: contains the codes, some downloaded annotation files, and a downloaded go ontology file [download]
• F2: contains all files in F1, and pre-computed results for methods: Resnik, Jiang, Lin, ISM_Resnik, ISM_Jiang, and ISM_Lin [download]
• F3: contains files used for evaluation on sequence similarity [download]
• F4: contains files used for evaluation on PPI [download]
• F5: contains files used for evaluation on cell cycle [download]

 

Directory Structure

Codes and intermediate results are organised as follows:

• All code is stored inthe directory 'CODE_Version4'
• The default go ontology file, and the intermediate results related to go trees are stored in the directory 'GO_TREE'.
• For an organism, the default go annotation file, and the parsed results are stored in the directory 'GENE_OrganismName', e.g. 'GENE_Yeast' for Yeast (Saccharomyces cerevisiae)
• For an organism, the related intermediate results are stored in the directory 'GO2OrganismName', e.g. 'GO2Yeast' for Yeast (Saccharomyces cerevisiae)

 

Some examples to run the codes

How to use F1

To use the function GeneSim and GoSim, you need to run INITIALIZE or DOALL first. DOALL is specially suited for users who want to use the whole genomic similarity for all the trees because it pre-computes all term similarities and gene product similarities for all genes in the three trees. However, if you are only interested in a very small gene set for a given tree, use INITIALIZE instead. Some examples are listed below.

a. Extract files to the decretory 'GO_SIM_V4'

b. In Matlab environment, enter the directory 'GO_SIM_V4/CODE_Version4'

c. There are 6 methods available in this code. They are coded as 6 numbers: 1,2,3,18,28, and 38 representing Resnik, Jiang, Lin, ISM_Resnik, ISM_Jiang, and ISM_Lin respectively. The three tree 'biological_process', 'cellular_component', and 'molecular_function' are coded as 1, 2, and 3. If you want results for the organism 'Yeast' for Resnik's method, run

Which_Tree=1; INITIALIZE(1,-1,1, -1, 1,1, 'Yeast', [1], -1,Which_Tree) 
or 
DOALL(1,-1,1, -1, 1,1, 'Yeast', [1], -1)

If you are curious about the parameter set, read the whole instruction or type  'help INITIALIZE' or 'help DOALL'

d. Then you can call function GeneSim to get the gene product similarity for a given gene list based on Resnik's method. For example, you have a gene list {'AAA1','AAC1','AAC2','AAC3'} and you are still in the directory 'GO_SIM_V4/CODE_Version4', and then run

SIM1 = GeneSim('..', {'AAA1','AAC1','AAC2','AAC3'}, 'biological_process', 1,'Yeast',-1)

You will get a similarity matrix on the gene list for biological_process based on Resnik's method

    7.4979    1.5213    1.5788    2.2474
    1.5213    8.3089    8.3089    8.3089
    1.5788    8.3089    9.0020    9.0020
    2.2474    8.3089    9.0020    9.0020

whose (i,j)-entry represents the semantic similarity between your i-th gene and j-th gene.  The first parameter is the location of your GO_SIM_V4; and in this example, assuming that you are still in the directory 'CODE_Version4', it is '..'

Run

GoList={'GO:0000001','GO:0000002','GO:0000003','GO:0000011','GO:0000019','GO:0000022'};
SIMILARITY = GoSim('..', GoList, 1, 1,'Yeast',-1)

You will get a similarity matrix on the GO term list for biological_process based on Resnik's method

         6.3279    4.1618    1.1590    5.4757    1.1590    2.6670
         4.1618    6.0316    1.1590    2.6670    1.1590    2.6670
         1.1590    1.1590    3.7393    1.1590    1.1590    1.1590
         5.4757    2.6670    1.1590    6.8048    1.1590    2.6670
         1.1590    1.1590    1.1590    1.1590    7.7493    1.1590
         2.6670    2.6670    1.1590    2.6670    1.1590    6.5597

Congratulation! Now you become a basic user of this code.  Up to now, you can obtain a similarity matrix based on Resnik for any give list in 'Yeast' for BP tree using the default setting for evidence codes and using the current ontology file and the annotation file.

Read the whole instruction to become an advanced user. Next you can exercise more.

e. If you want to a similarity matrix for 'cellular_component' and 'molecular_function' for the same gene list based on Resnik's method, run

SIM2 = GeneSim('..', {'AAA1','AAC1','AAC2','AAC3'}, 'cellular_component', 1,'Yeast',-1)
%if you have run DOALL in step c; otherwise, you need to first run
%Which_Tree=2; INITIALIZE(0,0,0, 0, 1,1, 'Yeast', [1], -1,Which_Tree)

SIM3 = GeneSim('..', {'AAA1','AAC1','AAC2','AAC3'}, 'molecular_function', 1,'Yeast',-1)
%if you have run DOALL in step c; otherwise, you need to first run
%Which_Tree=3; INITIALIZE(0,0,0, 0, 1,1, 'Yeast', [1], -1,Which_Tree) 

f. If you want to do similar thing as above, but you want to try the ISM_Resnik (code: 18), then run

Which_Tree=1; INITIALIZE(0,0,0,0, 0,0, 'Yeast', [18], -1,Which_Tree)  or  DOALL(0,0,0, 0, 0,0, 'Yeast', [18], -1)
SIM1 = GeneSim('..', {'AAA1','AAC1','AAC2','AAC3'}, 'biological_process', 18,'Yeast',-1)

Note that, assuming you have run step c, where some basic processes have been done for 'Yeast', you do not need to repeat them. This is why the first six parameters are set to 0. If you have not run step c before, then you need to run DOALL(1,-1,1, -1, 1,1, 'Yeast', [18], -1)  instead of DOALL(0,0,0, 0, 0,0, 'Yeast', [18], -1); or INITIALIZE(1,-1,1, -1, 1,1, 'Yeast', [18], -1,Which_Tree) instead of INITIALIZE(0,0,0,0, 0,0, 'Yeast', [18], -1,Which_Tree).

g. If you want to use the code further for other organisms such as Arabidopsis (Arabidopsis thaliana), Mouse (Mus musculus), Worm (Caenorhabditis elegans) and Fly (Drosophila melanogaster), then do the similar things in steps c-d. For example, for 'Arabidopsis' and for Resnik's method, run

Which_Tree=1;INITIALIZE(0,0,1, -1, 1,1, 'Arabidopsis', [1], -1,Which_Tree) or DOALL(0,0,1, -1, 1,1, 'Arabidopsis', [1], -1)
SIM1 = GeneSim('..', yourgenelist, 'biological_process', 1,'Yeast',-1)

Note that, assuming you have run step c, where some basic processes have been done for the GO Ontology, you do not need to repeat them. This is why the first two parameters are set to 0. If you have not run step c before, then you need to run DOALL(1,-1,1, -1, 1,1, 'Arabidopsis', [1], -1). 

h. For other organisms not in the list {Arabdopsis, Yeast, Mouse, Worm, Fly}, we did not provide you an annotation file, and you need to download the annotation file by yourself. For example, if you downloaded the annotation file for Ecoli (Escherichia coli) and extracted it as 'your_annotation_file', then you can run

Which_Tree=1;INITIALIZE(0,0,1, 'your_annotation_file', 1,1, 'ECOLI', [1], -1,Which_Tree)  or DOALL(0,0,1,'your_annotation_file', 1,1, 'ECOLI', [1], -1)
SIM1 = GeneSim('..', yourgenelist, 'biological_process', 1,'ECOLI',-1)

i. If you want to use the recent GO Ontology file to update the system, then the code can help download the recent GO Ontology file. Take 'Yeast' as an example, run

Which_Tree=1;INITIALIZE(1,0,1, -1, 1,1, 'Yeast', [1], -1,Which_Tree) or DOALL(1,0,1, -1, 1,1, 'Yeast', [1], -1)

Then, the code will download the recent GO Ontology file, and initialize the system.

j. If you have run (step c) already, and you do not want the default setting for evidence codes, then you can set your own evidence codes .For example, you want to ignore evidence codes IEA and NR, then you can run

Which_Tree=1;INITIALIZE(0,0,0, 0, 1,1, 'Yeast', [18], {'IEA', 'NR'},Which_Tree) or DOALL(0,0,0, 0, 1,1, 'Yeast', [18], {'IEA', 'NR'})

which means you do not parse the obo file and the annotation file again (because you did it in step c), and you ignore the annotations with evidence codes 'IEA' and 'NR', and you only want the result for the ISM_Resnik (18).

If you did not run (c) before, you want the same thing, then simply run

Which_Tree=1;INITIALIZE(1,-1,1, -1, 1,1, 'Yeast', [18], {'IEA', 'NR'}) or DOALL(1,-1,1, -1, 1,1, 'Yeast', [18], {'IEA', 'NR'})

Congratulation! Now you become an intermediate user of this code.  Up to now, you can obtain a similarity matrix based on any of the available methods for any given gene list in any organism  for any tree using any setting for evidence codes and using any version of the ontology file and any version of the annotation file.

How to use F2

All things are same as F1 except that it includes the intermediate results obtained by running

DOALL(1,-1,1, -1, 1,1, 'Yeast', [1,2,3,18,28,38], -1) ,

So you do not need the step c and f in F1.

 

How to use F3

0. Assume that you have downloaded F1, and initialized by running

DOALL(1,-1,1, -1, 1,1, 'Yeast', [1,2,3,18,28,38], -1) ,

Or you have download F2. 

1. Extract files to the directory 'Yeast_Similarity'

2. Entry the directory 'Yeast_Similarity', run

exp_yeast('../GO_SIM_V4',0)

To get the correlation between sequence similarity and semantic similarity WITHOUT the averaging procedure, where '../GO_SIM_V4' is the path where the directory 'GO_SIM_V4' is located. Here we assume that it is located in the parent directory. In your machine, please specify it according to where you put the GO_SIM_V4 code
3. Run

exp_yeast('../GO_SIM_V4',100)

To get the correlation between sequence similarity and semantic similarity WITH the averaging procedure, where 100 small intervals are created, and the means in these intervals are used to calculate the correlation.

How to use F4

0. Assume that you have downloaded F1, and initialized by running

DOALL(1,-1,1, -1, 1,1, 'Yeast', [1,2,3,18,28,38], -1) ,

Or you have download F2.

1. Extract files to the directory 'PPI'

2. Enter the directory 'PPI', run

for(method=[1,2,3,18,28,38]), experiments('../GO_SIM_V4',1,method,-1), end
for(method=[1,2,3,18,28,38]), experiments('../GO_SIM_V4',2,method,-1), end
for(method=[1,2,3,18,28,38]), experiments('../GO_SIM_V4',3,method,-1), end

where '../GO_SIM_V4' is the path where the directory 'GO_SIM_V4' is located. Here we assume that it is located in the parent directory. In your machine, please specify it according to where you put the GO_SIM_V4 code

3. Run

makepic(1, 100)

To generate the ROC curve for BP tree, in which the number of points in the curve is less than to equal to 100. Run

makepic(2, 100)

To get the ROC curve for CC tree, and

makepic(3, 100)

To get the ROC curve for MF tree.

4. Run

cal_auc(0.002)

To get the AUC for BP, CC, and MF

How to use F5

0. Assume that you have downloaded F1, and initialized by running

DOALL(1,-1,1, -1, 1,1, 'Yeast', [1,2,3,18,28,38], -1) ,

Or you have download F2.
1. Extract files to the directory Cell_Cylce.
2. Entry the directory Cell_Cylce, run
exp_cellcycle('../GO_SIM_V4',0)
to get the correlation between microarray correlation and semantic similarity WITHOUT the averaging procedure, where '../GO_SIM_V4' is the path where the directory 'GO_SIM_V4' is located. Here we assume that it is located in the parent directory. In your machine, please specify it according to where you put the GO_SIM_V4 code
3. Run
exp_cellcycle('../GO_SIM_V4',100)
to get the correlation between microarray correlation and semantic similarity WITH the averaging procedure, where 100 small intervals are created, and the means in these intervals are used to calculate the correlation.

Detailed Description of Some Functions