/*************************************************************************
* *
* This file is part of the 20n/act project. *
* 20n/act enables DNA prediction for synthetic biology/bioengineering. *
* Copyright (C) 2017 20n Labs, Inc. *
* *
* Please direct all queries to act@20n.com. *
* *
* This program is free software: you can redistribute it and/or modify *
* it under the terms of the GNU General Public License as published by *
* the Free Software Foundation, either version 3 of the License, or *
* (at your option) any later version. *
* *
* This program is distributed in the hope that it will be useful, *
* but WITHOUT ANY WARRANTY; without even the implied warranty of *
* MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the *
* GNU General Public License for more details. *
* *
* You should have received a copy of the GNU General Public License *
* along with this program. If not, see <http://www.gnu.org/licenses/>. *
* *
*************************************************************************/
package com.act.biointerpretation.cofactorremoval;
import act.server.NoSQLAPI;
import act.shared.Reaction;
import chemaxon.formats.MolImporter;
import com.act.biointerpretation.desalting.ReactionDesalter;
import com.act.biointerpretation.cofactorremoval.CofactorRemover;
import com.act.biointerpretation.cofactorremoval.CofactorsCorpus;
import com.act.biointerpretation.test.util.MockedNoSQLAPI;
import com.act.biointerpretation.test.util.TestUtils;
import org.junit.After;
import org.junit.Assert;
import org.junit.Before;
import org.junit.Test;
import org.mockito.MockitoAnnotations;
import java.util.ArrayList;
import java.util.Arrays;
import java.util.HashMap;
import java.util.List;
import java.util.Map;
import static org.junit.Assert.assertEquals;
import static org.junit.Assert.fail;
public class CofactorRemoverTest {
TestUtils utilsObject;
@Before
public void setUp() throws Exception {
// In case we ever use Mockito annotations, don't forget to initialize them.
MockitoAnnotations.initMocks(ReactionDesalter.class);
utilsObject = new TestUtils();
}
@After
public void tearDown() throws Exception {
}
@Test
public void testCofactorCorpusHasCorrectInchies() throws Exception {
CofactorsCorpus cofactorsCorpus = new CofactorsCorpus();
cofactorsCorpus.loadCorpus();
for (Map.Entry<String, String> inchiToName : cofactorsCorpus.getInchiToName().entrySet()) {
try {
MolImporter.importMol(inchiToName.getKey());
} catch (Exception e) {
Assert.fail(String.format("Error importing molecule from the inchi: %s with error message %s",
inchiToName.getKey(), e.getMessage()));
}
}
}
@Test
public void testReactionWithCofactorIsTransformedCorrectlyWhileReactionWithoutCofactorIsNottransformed() throws Exception {
List<Reaction> testReactions = new ArrayList<>();
Long[] products = {4L};
Map<Long, String> idToInchi = new HashMap<>();
// The first inchi is a cofactor while the second is not.
idToInchi.put(1L, "InChI=1/C10H15N4O15P3/c15-5-3(1-26-31(22,23)29-32(24,25)28-30(19,20)21)27-9(6(5)16)14-2-11-4-7(14)12-10(18)13-8(4)17/h2-3,5-6,9,15-16H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H2,12,13,17,18)");
idToInchi.put(2L, "InChI=1S/CH2O2/c2-1-3/h1H,(H,2,3)/p-1");
idToInchi.put(3L, "InChI=1S/C7H5Cl3/c8-4-5-2-1-3-6(9)7(5)10/h1-3H,4H2");
Long[] substrates1 = {1L, 3L};
Long[] substrates2 = {2L};
Integer[] substrateCoefficients1 = {2, 3};
Integer[] substrateCoefficients2 = {2};
Integer[] productCoefficients = {3};
Reaction testReaction1 =
utilsObject.makeTestReaction(substrates1, products, substrateCoefficients1, productCoefficients, true);
Reaction testReaction2 =
utilsObject.makeTestReaction(substrates2, products, substrateCoefficients2, productCoefficients, true);
testReactions.add(testReaction1);
testReactions.add(testReaction2);
MockedNoSQLAPI mockAPI = new MockedNoSQLAPI();
mockAPI.installMocks(testReactions, utilsObject.SEQUENCES, utilsObject.ORGANISM_NAMES, idToInchi);
NoSQLAPI mockNoSQLAPI = mockAPI.getMockNoSQLAPI();
CofactorRemover cofactorRemover = new CofactorRemover(mockNoSQLAPI);
cofactorRemover.init();
cofactorRemover.run();
assertEquals("Similar pre-cofactor removal substrates should be written as two entries", 2,
mockAPI.getWrittenReactions().size());
assertEquals("Since the first reaction had a cofactor in the substrates, there should one substrate after the cofactor" +
" is removed", 1, mockAPI.getWrittenReactions().get(0).getSubstrates().length);
assertEquals("Since the first reaction had a cofactor in the substrates, there should be one substrate coefficients after the cofactor" +
" is removed", 1, mockAPI.getWrittenReactions().get(0).getSubstrateIdsOfSubstrateCoefficients().size());
assertEquals("There should be one entry in the substrate cofactors list",
1, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors().length);
assertEquals("The substrate cofactor should match the correct substrate id",
1L, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[0].longValue());
assertEquals("The write substrate should match the correct read substrate id",
"InChI=1S/CH2O2/c2-1-3/h1H,(H,2,3)/p-1",
mockAPI.getWrittenChemicals().get(
mockAPI.getWrittenReactions().get(1).getSubstrates()[0].longValue()).getInChI());
assertEquals("Since the second reaction does not have a cofactor in the substrates, there should a substrate in the " +
"write db", 1, mockAPI.getWrittenReactions().get(1).getSubstrates().length);
assertEquals("There should be no entry in the substrate cofactors list",
0, mockAPI.getWrittenReactions().get(1).getSubstrateCofactors().length);
}
@Test
public void testAllCofactorsShouldBeRemoved() throws Exception {
List<Reaction> testReactions = new ArrayList<>();
Long[] products = {4L};
Map<Long, String> idToInchi = new HashMap<>();
// This is a rank 3 cofactor (should be removed)
String testInchi1 = "InChI=1/C10H15N4O15P3/c15-5-3(1-26-31(22,23)29-32(24,25)28-30(19,20)21)27-9(6(5)16)14-2-11-4-7(14)12-10(18)13-8(4)17/h2-3,5-6,9,15-16H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H2,12,13,17,18)";
idToInchi.put(1L, testInchi1);
// This is a rank 1 cofactor (should be removed)
String test2 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(2L, test2);
// This is a rank 1 cofactor (should be removed)
String test3 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(3L, test3);
Integer[] substrateCoefficients = {2, 3, 3};
Integer[] productCoefficients = {3};
Long[] substrates = {1L, 2L, 3L};
Reaction testReaction =
utilsObject.makeTestReaction(substrates, products, substrateCoefficients, productCoefficients, true);
testReactions.add(testReaction);
MockedNoSQLAPI mockAPI = new MockedNoSQLAPI();
mockAPI.installMocks(testReactions, utilsObject.SEQUENCES, utilsObject.ORGANISM_NAMES, idToInchi);
NoSQLAPI mockNoSQLAPI = mockAPI.getMockNoSQLAPI();
CofactorRemover cofactorRemover = new CofactorRemover(mockNoSQLAPI);
cofactorRemover.init();
cofactorRemover.run();
assertEquals("Similar pre-cofactor removal substrates should be written as one entry", 1,
mockAPI.getWrittenReactions().size());
assertEquals("The first reaction had 3 cofactors in the substrates, but there should be no substrates after the cofactor" +
" is removed", 0, mockAPI.getWrittenReactions().get(0).getSubstrates().length);
assertEquals("There should be three entries in the substrate cofactors list",
3, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors().length);
assertEquals("The substrate cofactor should match the correct substrate id",
testInchi1, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[0].longValue()).getInChI());
assertEquals("The substrate cofactor should match the correct substrate id",
test2, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[1].longValue()).getInChI());
assertEquals("The substrate cofactor should match the correct substrate id",
test3, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[2].longValue()).getInChI());
}
@Test
public void testExistingCofactorsAreNotOverwritten() throws Exception {
List<Reaction> testReactions = new ArrayList<>();
Long[] products = {4L};
Map<Long, String> idToInchi = new HashMap<>();
String testInchi1 = "InChI=1/C10H15N4O15P3/c15-5-3(1-26-31(22,23)29-32(24,25)28-30(19,20)21)27-9(6(5)16)14-2-11-4-7(14)12-10(18)13-8(4)17/h2-3,5-6,9,15-16H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H2,12,13,17,18)";
idToInchi.put(1L, testInchi1);
String test2 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(2L, test2);
String test3 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(3L, test3);
Integer[] substrateCoefficients = {2, 3};
Integer[] productCoefficients = {3};
Long[] substrates = {1L, 2L};
Reaction testReaction =
utilsObject.makeTestReaction(substrates, products, substrateCoefficients, productCoefficients, true);
// Set the third chemical as an existing cofactor to ensure it is not overwritten.
testReaction.setSubstrateCofactors(new Long[]{3L});
testReactions.add(testReaction);
MockedNoSQLAPI mockAPI = new MockedNoSQLAPI();
mockAPI.installMocks(testReactions, Arrays.asList(3L), utilsObject.SEQUENCES, utilsObject.ORGANISM_NAMES, idToInchi);
NoSQLAPI mockNoSQLAPI = mockAPI.getMockNoSQLAPI();
CofactorRemover cofactorRemover = new CofactorRemover(mockNoSQLAPI);
cofactorRemover.init();
cofactorRemover.run();
assertEquals("Similar pre-cofactor removal substrates should be written as one entry", 1,
mockAPI.getWrittenReactions().size());
assertEquals("The first reaction had 2 cofactors in the substrates, but there should be no substrates after the cofactor" +
" is removed", 0, mockAPI.getWrittenReactions().get(0).getSubstrates().length);
assertEquals("There should be three entries in the substrate cofactors list",
3, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors().length);
assertEquals("The substrate cofactor that was already in the reaction should persist and appear first",
test3, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[0].longValue()).getInChI());
assertEquals("The substrate cofactor should match the correct substrate id",
testInchi1, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[1].longValue()).getInChI());
assertEquals("The substrate cofactor should match the correct substrate id",
test2, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[2].longValue()).getInChI());
}
@Test
public void testReactionWithNoEffectIsNotWritten() throws Exception {
List<Reaction> testReactions = new ArrayList<>();
Map<Long, String> idToInchi = new HashMap<>();
String testInchi1 = "InChI=1/C10H15N4O15P3/c15-5-3(1-26-31(22,23)29-32(24,25)28-30(19,20)21)27-9(6(5)16)14-2-11-4-7(14)12-10(18)13-8(4)17/h2-3,5-6,9,15-16H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H2,12,13,17,18)";
idToInchi.put(1L, testInchi1);
Integer[] substrateCoefficients = {3};
Integer[] productCoefficients = {3};
Long[] substrates = {1L};
Long[] products = {1L};
Reaction testReaction =
utilsObject.makeTestReaction(substrates, products, substrateCoefficients, productCoefficients, true);
// Set the third chemical as an existing cofactor to ensure it is not overwritten.
testReaction.setSubstrateCofactors(new Long[]{3L});
testReactions.add(testReaction);
MockedNoSQLAPI mockAPI = new MockedNoSQLAPI();
mockAPI.installMocks(testReactions, utilsObject.SEQUENCES, utilsObject.ORGANISM_NAMES, idToInchi);
NoSQLAPI mockNoSQLAPI = mockAPI.getMockNoSQLAPI();
CofactorRemover cofactorRemover = new CofactorRemover(mockNoSQLAPI);
cofactorRemover.init();
cofactorRemover.run();
assertEquals("A reaction that imparts no change to its substrate should not be written", 0,
mockAPI.getWrittenReactions().size());
}
@Test
public void testReactionThatChangesOnlyCofactorsIsStillWritten() throws Exception {
List<Reaction> testReactions = new ArrayList<>();
Map<Long, String> idToInchi = new HashMap<>();
String testInchi1 = "InChI=1/C10H15N4O15P3/c15-5-3(1-26-31(22,23)29-32(24,25)28-30(19,20)21)27-9(6(5)16)14-2-11-4-7(14)12-10(18)13-8(4)17/h2-3,5-6,9,15-16H,1H2,(H,22,23)(H,24,25)(H2,19,20,21)(H2,12,13,17,18)";
idToInchi.put(1L, testInchi1);
String test2 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(2L, test2);
String test3 = "InChI=1/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)";
idToInchi.put(3L, test3);
Integer[] substrateCoefficients = {1};
Integer[] productCoefficients = {1};
Long[] substrates = {1L};
Long[] products = {1L};
Reaction testReaction =
utilsObject.makeTestReaction(substrates, products, substrateCoefficients, productCoefficients, true);
// Set the third chemical as an existing cofactor to ensure it is not overwritten.
testReaction.setSubstrateCofactors(new Long[]{2L});
testReaction.setProductCofactors(new Long[]{3L});
testReactions.add(testReaction);
MockedNoSQLAPI mockAPI = new MockedNoSQLAPI();
mockAPI.installMocks(testReactions, Arrays.asList(2L, 3L), utilsObject.SEQUENCES, utilsObject.ORGANISM_NAMES, idToInchi);
NoSQLAPI mockNoSQLAPI = mockAPI.getMockNoSQLAPI();
CofactorRemover cofactorRemover = new CofactorRemover(mockNoSQLAPI);
cofactorRemover.init();
cofactorRemover.run();
assertEquals("Similar pre-cofactor removal substrates should be written as one entry", 1,
mockAPI.getWrittenReactions().size());
assertEquals("The first reaction had 1 coenzyme in the substrates, " +
"but there should be no substrates after the cofactor is removed",
0, mockAPI.getWrittenReactions().get(0).getSubstrates().length);
assertEquals("The first reaction had 1 coenzyme in the products, " +
"but there should be no products after the cofactor is removed",
0, mockAPI.getWrittenReactions().get(0).getProducts().length);
assertEquals("The old substrate/product should now exist as a coenzyme",
testInchi1, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getCoenzymes()[0].longValue()).getInChI());
assertEquals("The original substrate cofactor should remain",
1, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors().length);
assertEquals("The substrate cofactor that was already in the reaction should persist",
test2, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getSubstrateCofactors()[0].longValue()).getInChI());
assertEquals("The original product cofactor should remain",
1, mockAPI.getWrittenReactions().get(0).getSubstrateCofactors().length);
assertEquals("The product cofactor should match the correct substrate id",
test3, mockAPI.getWrittenChemicals().get(mockAPI.getWrittenReactions().get(0).getProductCofactors()[0].longValue()).getInChI());
}
}