This repository provides an implementation described in the papers: https://link.springer.com/article/10.1186/s12859-019-3296-1 and https://link.springer.com/chapter/10.1007/978-3-030-80418-3_26.
SS: Taxonomic Semantic Similarity; ES: Embedding Semantic Similarity; SSM: Semantic Similarity Measure; GP: Genetic Programming; GO: Gene Ontology; PPI: Protein-Protein Interaction.
In recent years, biomedical ontologies have become important for describing existing biological knowledge in the form of knowledge graphs. Data mining approaches that work with knowledge graphs have been proposed, but they are based on vector representations that do not capture the full underlying semantics. An alternative is to use machine learning approaches that explore semantic similarity. However, since ontologies can model multiple perspectives, semantic similarity computations for a given learning task need to be fine-tuned to account for this. Obtaining the best combination of semantic similarity aspects for each learning task is not trivial and typically depends on expert knowledge.
We have developed a novel approach, evoKGsim, that applies Genetic Programming over a set of semantic similarity features, each based on a semantic aspect of the data, to obtain the best combination for a given supervised learning task. The approach was evaluated on several benchmark datasets for protein-protein interaction prediction using the Gene Ontology as the knowledge graph to support semantic similarity, and it outperformed competing strategies, including manually selected combinations of semantic aspects emulating expert knowledge. evoKGsim was also able to learn species-agnostic models with different combinations of species for training and testing, effectively addressing the limitations of predicting protein-protein interactions for species with fewer known interactions.
evoKGsim can overcome one of the limitations in knowledge graph-based semantic similarity applications: the need to expertly select which aspects should be taken into account for a given application. Applying this methodology to protein-protein interaction prediction proved successful, paving the way to broader applications.
- install python 3.6.8;
- install java JDK 11.0.4;
- install python libraries by running the following command:
pip install -r req.txt.
For the program to work, provide a text file with the protein pairs and respective labels (interact or non-interact). This tab-delimited text file have 3 columns:
- 1st column - Protein1 UniProt Identifier;
- 2nd column - Protein2 UniProt Identifier;
- 3rd column - Label (the options are 1 for interacting pairs and 0 for non-interacting pairs).
In this work, we used 9 Benchmark datasets (STRING-SC, STRING-HS, STRING-EC, STRING-DM, DIP-HS, BIND-SC, DIP/MIPS-SC, GRID/HPRD-bal-HS, and GRID/HPRD-unbal-HS) of different species for evaluation. The data is in Data/PPIdatasets folder.
For taxonomic semantic similarity calculation, provide:
- Dataset file with the previously described format;
- Ontology file in OWL format;
- Annotations file in 2.0. or 2.1. GAF format (http://geneontology.org/docs/go-annotation-file-gaf-format-2.0/). GAFs are tab-delimited plain text files, where each line in the file represents a single association between a gene product and a GO term.
To support SS calculations, SML was employed:
The Semantic Measures Library and Toolkit: fast computation of semantic similarity and relatedness using biomedical ontologies
Sébastien Harispe*, Sylvie Ranwez, Stefan Janaqi and Jacky Montmain
Bioinformatics 2014 30(5): 740-742. doi: 10.1093/bioinformatics/btt581
The software is available on GitHub (https://github.com/sharispe/slib/tree/dev/slib-sml) under a CeCILL License.
In Linux, compile the command:
javac -cp ".:./SS_Calculation/jar_files/*" ./SS_Calculation/Run_SS_calculation.java
and then run
java -cp ".:./SS_Calculation/jar_files/*" SS_Calculation/Run_SS_calculation
This command will create, for each dataset, SS files (one for each SSM) with the SS between each pair of proteins for each semantic aspect (biological process, cellular component and molecular function) using six different SSMs (ResnikMax_ICSeco, ResnikMax_ICResnik, ResnikBMA_ICSeco, ResnikBMA_ICResnik, simGIC_ICSeco, simGIC_ICResnik). The description of this text file is in SS_Calculation/SS_files/SS_file_ format.txt file. The new SS files are placed in SS_Calculation/SS_files/datasetname folder.
An RDF2Vec python implementation was used to calculate graph embedding.
RDF2Vec: RDF graph embeddings for data mining
Petara Ristoski and Heiko Paulheim
International Semantic Web Conference, Springer, Cham, 2016 (pp. 498-514)
The implementation is available on GitHub https://github.com/IBCNServices/pyRDF2Vec.
In RDF2Vec, a set of sequences was generated from Weisfeiler-Lehman subtree kernels. For the Weisfeiler-Lehman algorithm, we use walks with depth 8, and we extracted a limited number of 500 random walks for each protein. The corpora of sequences were used to build a Skip-Gram model with the following parameters: window size=5; number of iterations=10; entity vector size=200.
Run the command to calculate the embeddings for each protein using rdf2vec implementation:
python3 SS_Embedding_Calculation/run_RDF2VecEmbeddings_PPI.py
For each dataset:
- This command creates 3 embedding files (one for each GO semantic apect: biological_process, cellular_component aspect, molecular_function) and place them in [SS_Embedding_Calculation/Embeddings/datasetname/aspect] (https://github.com/ritatsousa/evoKGsim/tree/master/SS_Embedding_Calculation/Embeddings) folder. The filename is in the format “Embeddings_datasetname_skig-gram_wl_aspect.txt”. The description of this text file is in SS_Embedding_Calculation/Embeddings/Embeddings_format.txt file.
OpenKE is only implemented for the Linux system.
Run the command to calculate the embeddings for each protein using OpenKE implementation for 6 embedding methods (TransE, TransH, TransD, TransR, distMult, ComplEx):
python3 SS_Embedding_Calculation/run_model_PPI.py
For each dataset:
- For each embedding method, this command creates 3 embedding files (one for each GO semantic apect: biological_process, cellular_component aspect, molecular_function) and place them in [SS_Embedding_Calculation/Embeddings/datasetname/aspect] (https://github.com/ritatsousa/evoKGsim/tree/master/SS_Embedding_Calculation/Embeddings) folder. The filename is in the format “Embeddings_datasetname_method_aspect.txt”. The description of this text file is in SS_Embedding_Calculation/Embeddings/Embeddings_format.txt file.
After generating embeddings for each semantic aspect and then calculated the cosine similarity for each pair in datasets. Run the command for calculating embedding similarity for each semantic aspect (biological process ES_BP, cellular component ES_CC and molecular function ES_MF):
python3 SS_Embedding_Calculation/run_embedSS_calculation.py
For each dataset:
- This command creates 1 embedding similarity file and places it in [SS_Embedding_Calculation/Embeddings_SS_files] (https://github.com/ritatsousa/evoKGsim/tree/master/SS_Embedding_Calculation/Embeddings_SS_files) folder. The filename is in the format "embedss_200_model_datasetname.txt". The format of each line of embedding similarity file is "Prot1 Prot2 ES_BP ES_CC ES_MF";
For 10-cross-validation purposes, run the command to split each dataset into ten partitions:
python3 Prediction/run_make_shuffle_partitions.py
This command will create, for each dataset, 10 Partitions files and place them in Prediction/Results/Datasetname/Shuffle_Partitions folder. Each line of these files is an index (corresponding to a protein pair) of the dataset. This folder is already created, so you do not have to change any folder path.
With semantic similarities, run the command for PPI prediction using evolved combinations:
python3 Prediction/run_withPartitions_evoKGsim.py
The parameters we have set are listed in the next Table. All others were used with the default values of the gplearn software.
| Parameter | Value |
|---|---|
| Number of generations | 50 |
| Size of population | 500 |
| Function set | +,-,/,x,max,min |
| Fitness function | RMSE |
| Parsimony coeffcient | 0.00001 |
For running the baselines (static combinations of semantic aspects), run the command:
python3 Prediction/run_withPartitions_evoKGsim_SS.py False True
@article {PMID:31900127,
Title = {Evolving knowledge graph similarity for supervised learning in complex biomedical domains},
Author = {Sousa, Rita T and Silva, Sara and Pesquita, Catia},
DOI = {10.1186/s12859-019-3296-1},
Number = {1},
Volume = {21},
Month = {January},
Year = {2020},
Journal = {BMC bioinformatics},
ISSN = {1471-2105},
Pages = {6},
URL = {https://europepmc.org/articles/PMC6942314},
}