Extend MixtureFinder to codon, binary, multistate, (and amino acid) data

main/phylotesting.cpp

@@ -6207,6 +6207,16 @@ void addModel(string model_str, string& new_model_str, string new_subst) {
     }
 }
 
+// initialise model frequency set in MixtureFinder for different sequence types
+char* initFreqSet(SeqType seq_type) {
+    switch (seq_type) {
+        case SEQ_CODON:   return ",F1X4,F3X4";
+        case SEQ_MORPH:   return "FQ";
+        case SEQ_PROTEIN: return ",FO";
+        default:          return "FO";
+    }
+}
+
 /**
  @brief Find the best component of a Q-mixture model while fixing other components
  @note This function is similar to runModelFinder, but it is adapted for optimisation of Q-Mixture model
@@ -6355,8 +6365,8 @@ CandidateModel findMixtureComponent(Params &params, IQTree &iqtree, ModelCheckpo
             }
         }
         skip_all_when_drop = true;
-    } else if (mixture_action == MA_FIND_CLASS) {
-        char init_state_freq_set[] = "FO";
+      } else if (mixture_action == MA_FIND_CLASS) {
+        char* init_state_freq_set = initFreqSet(iqtree.aln->seq_type);
         if (!params.state_freq_set) {
             params.state_freq_set = init_state_freq_set;
         }
@@ -6527,7 +6537,7 @@ void runMixtureFinderMain(Params &params, IQTree* &iqtree, ModelCheckpoint &mode
     double LR, df_diff, pvalue;
     string criteria_str;
 
-    char init_state_freq_set[] = "FO";
+    char* init_state_freq_set = initFreqSet(iqtree->aln->seq_type);
     if (!params.state_freq_set) {
         params.state_freq_set = init_state_freq_set;
     }
@@ -6538,15 +6548,26 @@ void runMixtureFinderMain(Params &params, IQTree* &iqtree, ModelCheckpoint &mode
 
     // Step 0: (reorder candidate DNA models when -mset is used) build the nest-relationship network
     map<string, vector<string> > nest_network;
-    if (iqtree->aln->seq_type == SEQ_DNA) {
-        StrVector model_names, freq_names;
-        getModelSubst(iqtree->aln->seq_type, iqtree->aln->isStandardGeneticCode(), params.model_name,
-                      params.model_set, params.model_subset, model_names);
-        getStateFreqs(iqtree->aln->seq_type, params.state_freq_set, freq_names);
+    StrVector model_names, freq_names;
+    getModelSubst(iqtree->aln->seq_type, iqtree->aln->isStandardGeneticCode(), params.model_name,
+                  params.model_set, params.model_subset, model_names);
+    getStateFreqs(iqtree->aln->seq_type, params.state_freq_set, freq_names);
+
+    auto isOnlyMKAndFQ = [&]() -> bool {
+        bool onlyMK = std::all_of(model_names.begin(), model_names.end(),
+            [](const std::string& s) { return s == "MK"; });
+        bool onlyFQ = std::all_of(freq_names.begin(), freq_names.end(),
+            [](const std::string& s) { return s == "+FQ"; });
+        return onlyMK && onlyFQ;
+    };
+    if (isOnlyMKAndFQ()) {
+        outError("Error! Running MixtureFinder only with the MK model and the FQ frequency is completely meaningless.\nPlease provide additional models and/or frequencies, such as GTRX, +F, and +FO, using -mset and/or -mfreq, if you really want to use MixtureFinder for your multistate data.");
+    }
 
+    if (iqtree->aln->seq_type == SEQ_DNA) {
         nest_network = generateNestNetwork(model_names, freq_names);
     }
-
+    
     // Step 1: run ModelFinder
     params.model_name = "";
     bool under_mix_finder = true;
@@ -6651,8 +6672,14 @@ void runMixtureFinder(Params &params, IQTree* &iqtree, ModelCheckpoint &model_in
         outError("Error! The option -m '" + params.model_name + "' cannot work on data set with partitions");
 
     if (iqtree->aln->seq_type != SEQ_DNA)
-        outError("Error! The option -m '" + params.model_name + "' can only work on DNA data set");
-
+        outWarning("MixtureFinder has not been tested for non-DNA data types. Be cautious about interpreting the results");
+
+    if (iqtree->aln->getMaxNumStates() > 6)
+        outWarning("Running MixtureFinder for the given data type can take much time. Please consider restricting the set of the models to test as much as possible");
+
+    if (iqtree->aln->seq_type == SEQ_PROTEIN && !params.force_aa_mix_finder)
+        outError("Error! We already have the mixture frequency vectors C10–C60 which are effective for modeling amino acid data.\nPlease make sure running MixtureFinder for your amino acid data makes sense.\nIf you are determined to do that, please add an option --force-aa-mix-finder to the command line.");
+
     cout << "--------------------------------------------------------------------" << endl;
     cout << "|                Running MixtureFinder                             |" << endl;
     cout << "--------------------------------------------------------------------" << endl;

model/modelmixture.cpp

@@ -1403,6 +1403,8 @@ void ModelMixture::initMixture(string orig_model_name, string model_name, string
                     } else {
                         outError("The user defined frequency model is incorrect");
                     }
+                } else if (fstr == "+FU" || fstr == "+Fu") {
+                    model_freq = FREQ_USER_DEFINED;
                 } else if (fstr == "+FO" || fstr == "+Fo") {
                     model_freq = FREQ_ESTIMATE;
                 } else if (fstr == "+FQ" || fstr == "+Fq") {

model/modelmorphology.cpp

@@ -30,9 +30,11 @@ void ModelMorphology::init(const char *model_name, string model_params, StateFre
 		}
         num_params = 0;
     } else if (name == "GTR" || name == "GTRX") {
-        outWarning("GTRX multistate model will estimate " + convertIntToString(getNumRateEntries()-1) + " substitution rates that might be overfitting!");
-        outWarning("Please only use GTRX with very large data and always test for model fit!");
-        name = "GTRX";
+			if (num_states > 6 || phylo_tree->aln->getNPattern() < 100) {
+				outWarning("GTRX multistate model will estimate " + convertIntToString(getNumRateEntries()-1) + " substitution rates that might be overfitting for the length of your alignment/partition!");
+				outWarning("Please only use GTRX with large data and always test for model fit!");
+			}
+			name = "GTRX";
 	} else {
 		// if name does not match, read the user-defined model
 		readParameters(model_name);
@@ -122,20 +124,22 @@ string ModelMorphology::getName() {
 }
 
 string ModelMorphology::getNameParams(bool show_fixed_params) {
-    if (num_params == 0) return name;
     ostringstream retname;
     size_t pos_plus = name.find('+');
     if (pos_plus != string::npos) {
-        retname << name.substr(0, pos_plus) << '{';
+        retname << name.substr(0, pos_plus);
     } else {
-        retname << name << '{';
+        retname << name;
     }
-    int nrates = getNumRateEntries();
-    for (int i = 0; i < nrates; i++) {
-        if (i>0) retname << ',';
-        retname << rates[i];
+    if (num_params > 0 || show_fixed_params) {
+        retname << '{';
+        int nrates = getNumRateEntries();
+        for (int i = 0; i < nrates; i++) {
+            if (i > 0) retname << ',';
+            retname << rates[i];
+        }
+        retname << '}';
     }
-    retname << '}';
     if (pos_plus != string::npos) {
         retname << name.substr(pos_plus);
     } else {

utils/tools.cpp

@@ -1487,6 +1487,7 @@ void parseArg(int argc, char *argv[], Params &params) {
     params.ignore_checkpoint = false;
     params.checkpoint_dump_interval = 60;
     params.force_unfinished = false;
+    params.force_aa_mix_finder = false;
     params.print_all_checkpoints = false;
     params.suppress_output_flags = 0;
     params.ufboot2corr = false;
@@ -5475,6 +5476,11 @@ void parseArg(int argc, char *argv[], Params &params) {
 				params.force_unfinished = true;
 				continue;
 			}
+
+      if (strcmp(argv[cnt], "-force-aa-mix-finder") == 0 || strcmp(argv[cnt], "--force-aa-mix-finder") == 0) {
+        params.force_aa_mix_finder = true;
+        continue;
+      }
 
 			if (strcmp(argv[cnt], "-cptime") == 0 || strcmp(argv[cnt], "--cptime") == 0) {
 				cnt++;

utils/tools.h

@@ -2453,6 +2453,9 @@ class Params {
     /** true if ignoring the "finished" flag in checkpoint file */
     bool force_unfinished;
 
+    /** true if forcing IQ-TREE to run MixtureFinder for amino acid data */
+    bool force_aa_mix_finder;
+
     /** TRUE to print checkpoints to 1.ckp.gz, 2.ckp.gz,... */
     bool print_all_checkpoints;