section 4.2.4 MTMAMΒΆ

This is another example from section 4.2.4 of Molecular Evolution: A Statistical Approach, page 109.

It computes the log likelihood for the empirical MTMAM model of molecular evolution for an evolutionary tree of primates.

The conditional expected number of transitions per edge divided by the conditional expected exit rate from each state can be used to iteratively update the parameters corresponding to edge-specific rate scaling factors, reaching the -14,558.59 log likelihood after six iterations. This is an expectation maximization.

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from __future__ import print_function, division, absolute_import

import copy
import json

import numpy as np
from numpy.testing import assert_equal

import jsonctmctree.interface

s_mtmam = """\
 32                                                                         
  2   4                                                                     
 11   0 864                                                                 
  0 186   0   0                                                             
  0 246   8  49   0                                                         
  0   0   0 569   0 274                                                     
 78  18  47  79   0   0  22                                                 
  8 232 458  11 305 550  22   0                                             
 75   0  19   0  41   0   0   0   0                                         
 21   6   0   0  27  20   0   0  26 232                                     
  0  50 408   0   0 242 215   0   0   6   4                                 
 76   0  21   0   0  22   0   0   0 378 609  59                             
  0   0   6   5   7   0   0   0   0  57 246   0  11                         
 53   9  33   2   0  51   0   0  53   5  43  18   0  17                     
342   3 446  16 347  30  21 112  20   0  74  65  47  90 202                 
681   0 110   0 114   0   4   0   1 360  34  50 691   8  78 614             
  5  16   6   0  65   0   0   0   0   0  12   0  13   0   7  17   0         
  0   0 156   0 530  54   0   1 1525 16  25  67   0 682   8 107   0  14    
398   0   0  10   0  33  20   5   0 2220 100  0 832   6   0   0 237   0   0\
"""


s_distn = """
0.0692 0.0184 0.0400 0.0186 0.0065 0.0238 0.0236 0.0557 0.0277 0.0905
0.1675 0.0221 0.0561 0.0611 0.0536 0.0725 0.0870 0.0293 0.0340 0.0428
"""

s_aas = 'ARNDCQEGHILKMFPSTWYV'

def main():
    nstates = len(s_aas)
    assert_equal(nstates, 20)
    d = {a : i for i, a in enumerate(s_aas)}
    distn = [float(x) for x in s_distn.strip().split()]
    assert_equal(len(distn), nstates)
    lines = s_mtmam.splitlines()
    assert_equal(len(lines), nstates-1)
    rate_matrix = np.zeros((nstates, nstates), dtype=int)
    for i, line in enumerate(lines):
        row_index = i + 1
        row = [int(x) for x in line.strip().split()]
        assert_equal(len(row), row_index)
        rate_matrix[row_index, :row_index] = row
    rate_matrix = np.multiply(rate_matrix + rate_matrix.T, distn)
    exit_rates = rate_matrix.sum(axis=1)

    # This is a partial scene, missing the root distribution,
    # the process definition, and the observed data.
    scene = {
            "node_count" : 12,
            "process_count" : 1,
            "state_space_shape" : [20],
            "tree" : {
                "row_nodes" : [
                    0, 7, 7, 8, 8, 9, 9, 10, 10, 11, 11],
                "column_nodes" : [
                    8, 1, 2, 7, 9, 3, 10, 6, 11, 4, 5],
                "edge_rate_scaling_factors" : [
                    0.001, 0.001, 0.001, 0.001, 0.001, 0.001,
                    0.001, 0.001, 0.001, 0.001, 0.001],
                "edge_processes" : [
                    0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0]
                }
            }

    # Add the root distribution.
    scene['root_prior'] = {
            "states" : [[i] for i in range(nstates)],
            "probabilities" : distn
            }

    # Add the process definition.
    triples = []
    for i in range(nstates):
        for j in range(nstates):
            r = rate_matrix[i, j]
            if i != j and r:
                triples.append((i, j, r))
    row_states, col_states, rates = zip(*triples)
    scene['process_definitions'] = [{
        "row_states" : [[s] for s in row_states],
        "column_states" : [[s] for s in col_states],
        "transition_rates" : rates
        }]

    # Add the observed data.
    sequences = []
    with open('mtCDNApri.aa') as fin:
        lines = fin.readlines()
        header = lines[0]
        for line in lines[1:]:
            name, sequence = line.strip().split()
            sequences.append([d[x] for x in sequence])
    columns = [list(x) for x in zip(*sequences)]
    nsites = len(columns)
    scene['observed_data'] = {
            "nodes" : [0, 1, 2, 3, 4, 5, 6],
            "variables" : [0, 0, 0, 0, 0, 0, 0],
            "iid_observations" : columns
            }

    # Define some requests.
    # These include the log likelihood,
    # some dwell time expectations, and some transition count expectations.
    requests = [
            {"property" : "SNNLOGL"},
            {
                "property" : "SDWDWEL",
                "state_reduction" : {
                    "states" : [[i] for i in range(nstates)],
                    "weights" : exit_rates.tolist()
                }
            },
            {
                "property" : "SDNTRAN",
                "transition_reduction" : {
                    "row_states" : [[s] for s in row_states],
                    "column_states" : [[s] for s in col_states],
                    "weights" : [1] * len(triples)
                }
            }]

    # Request some stuff.
    j_in = {
            "scene" : scene,
            "requests" : requests
            }

    arr = []
    j_out = None
    for i in range(7):
        if j_out is None:
            j_out = jsonctmctree.interface.process_json_in(j_in)
        else:
            dwells = j_out['responses'][1]
            transitions = j_out['responses'][2]
            scaling_factors = [t/d for t, d in zip(transitions, dwells)]
            j_in['scene']['tree']['edge_rate_scaling_factors'] = scaling_factors
            j_out = jsonctmctree.interface.process_json_in(j_in)
        arr.append(copy.deepcopy(j_out))

    print(json.dumps(arr, indent=4))


main()
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[
    {
        "status": "feasible", 
        "responses": [
            -16504.121032993055, 
            [
                390460.1059915314, 
                390424.5844230256, 
                391224.60535462154, 
                390824.8875002111, 
                390697.27993762447, 
                390043.24810754554, 
                390554.30746285967, 
                390649.92327320843, 
                389776.7310744418, 
                389136.96053040074, 
                388944.61400367785
            ], 
            [
                95.79212073378258, 
                61.93135540104879, 
                60.24470946801712, 
                72.95137332382043, 
                74.8324931106707, 
                114.68492421659182, 
                131.4201313568659, 
                230.46271166866788, 
                201.85718287482823, 
                113.2558893397393, 
                102.61130105420631
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14615.45177721429, 
            [
                390329.090286233, 
                390266.26908660866, 
                391066.39607547666, 
                390611.3625268762, 
                390524.70785371325, 
                389931.06101992645, 
                390351.1126739523, 
                390499.7650051904, 
                389459.55536128406, 
                388892.806748215, 
                388701.9705687931
            ], 
            [
                73.70766635159143, 
                38.18459705173582, 
                35.316752969600415, 
                43.078659444371354, 
                37.97967486227084, 
                89.13839402137754, 
                93.82513950950059, 
                217.02806583421844, 
                179.5893615119534, 
                87.72147690595901, 
                70.28055492514683
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14559.544636017676, 
            [
                390328.61872730206, 
                390254.32603035594, 
                391054.73439382075, 
                390600.5686739526, 
                390552.6731726354, 
                389956.3666851394, 
                390395.35882293235, 
                390516.58402257576, 
                389456.21133322164, 
                388870.1013831647, 
                388680.18994273257
            ], 
            [
                74.47857833147525, 
                37.87478016778081, 
                34.5555552841812, 
                40.995137533150285, 
                33.042365140020976, 
                90.80469992743372, 
                87.98117910994463, 
                217.92673877299362, 
                179.02334833050713, 
                87.9519282620357, 
                66.95304311276284
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14558.679492389878, 
            [
                390327.18704844266, 
                390252.11766812106, 
                391052.5501532332, 
                390596.7203876089, 
                390561.4667511602, 
                389966.79685595026, 
                390416.48503409344, 
                390528.2576211807, 
                389464.82133761985, 
                388867.6363936431, 
                388677.6635125758
            ], 
            [
                74.9180216155701, 
                37.89988987007537, 
                34.522729385014436, 
                40.66327688510903, 
                31.70563683058224, 
                92.13453901806906, 
                86.60930481714882, 
                218.5168970329599, 
                179.50084156422488, 
                88.46335584529685, 
                66.27857440209739
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14558.604011930442, 
            [
                390326.3472349087, 
                390251.4306210645, 
                391051.87252850796, 
                390595.1125301453, 
                390564.2062571244, 
                389970.5063065846, 
                390424.09742512205, 
                390532.5646433043, 
                389468.47017160396, 
                388867.2068578355, 
                388677.19180607935
            ], 
            [
                75.04424767171336, 
                37.90244282411175, 
                34.522795173905514, 
                40.58652860788022, 
                31.259257663704524, 
                92.63978474704587, 
                86.23039258851394, 
                218.6998496012418, 
                179.73012202094094, 
                88.63464270632278, 
                66.09143469841817
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14558.59572822224, 
            [
                390326.0002153936, 
                390251.20633083815, 
                391051.6521278921, 
                390594.5170990737, 
                390565.1258302591, 
                389971.81857915595, 
                390426.77312118816, 
                390534.05067966715, 
                389469.7970711172, 
                388867.1093589269, 
                388677.08085152676
            ], 
            [
                75.0808895141623, 
                37.90229913040323, 
                34.523694320534304, 
                40.56723880147044, 
                31.10348951003328, 
                92.81602807303793, 
                86.12107550833387, 
                218.75005119403716, 
                179.81468114217932, 
                88.68620712347064, 
                66.03581896848449
            ]
        ]
    }, 
    {
        "status": "feasible", 
        "responses": [
            -14558.594786234356, 
            [
                390325.86895244475, 
                390251.13295395265, 
                391051.58020462503, 
                390594.30511277943, 
                390565.4422909194, 
                389972.28152996185, 
                390427.7080287603, 
                390534.5573468209, 
                389470.2646910455, 
                388867.08596201823, 
                388677.0534854288
            ], 
            [
                75.09203425335421, 
                37.90219174533584, 
                34.52400997815937, 
                40.56224880903427, 
                31.048668496080666, 
                92.87676799816758, 
                86.08922785361307, 
                218.76314629525257, 
                179.84374455303276, 
                88.70164218119001, 
                66.01901840002965
            ]
        ]
    }
]

And using the generic edge rate EM in the ‘extras’ module:

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from __future__ import print_function, division, absolute_import

import numpy as np
from numpy.testing import assert_equal

from jsonctmctree.interface import process_json_in
from jsonctmctree.extras import optimize_em

s_mtmam = """\
 32                                                                         
  2   4                                                                     
 11   0 864                                                                 
  0 186   0   0                                                             
  0 246   8  49   0                                                         
  0   0   0 569   0 274                                                     
 78  18  47  79   0   0  22                                                 
  8 232 458  11 305 550  22   0                                             
 75   0  19   0  41   0   0   0   0                                         
 21   6   0   0  27  20   0   0  26 232                                     
  0  50 408   0   0 242 215   0   0   6   4                                 
 76   0  21   0   0  22   0   0   0 378 609  59                             
  0   0   6   5   7   0   0   0   0  57 246   0  11                         
 53   9  33   2   0  51   0   0  53   5  43  18   0  17                     
342   3 446  16 347  30  21 112  20   0  74  65  47  90 202                 
681   0 110   0 114   0   4   0   1 360  34  50 691   8  78 614             
  5  16   6   0  65   0   0   0   0   0  12   0  13   0   7  17   0         
  0   0 156   0 530  54   0   1 1525 16  25  67   0 682   8 107   0  14    
398   0   0  10   0  33  20   5   0 2220 100  0 832   6   0   0 237   0   0\
"""


s_distn = """
0.0692 0.0184 0.0400 0.0186 0.0065 0.0238 0.0236 0.0557 0.0277 0.0905
0.1675 0.0221 0.0561 0.0611 0.0536 0.0725 0.0870 0.0293 0.0340 0.0428
"""

s_aas = 'ARNDCQEGHILKMFPSTWYV'

def main():
    nstates = len(s_aas)
    assert_equal(nstates, 20)
    d = {a : i for i, a in enumerate(s_aas)}
    distn = [float(x) for x in s_distn.strip().split()]
    assert_equal(len(distn), nstates)
    lines = s_mtmam.splitlines()
    assert_equal(len(lines), nstates-1)
    rate_matrix = np.zeros((nstates, nstates), dtype=int)
    for i, line in enumerate(lines):
        row_index = i + 1
        row = [int(x) for x in line.strip().split()]
        assert_equal(len(row), row_index)
        rate_matrix[row_index, :row_index] = row
    rate_matrix = np.multiply(rate_matrix + rate_matrix.T, distn)
    exit_rates = rate_matrix.sum(axis=1)

    # This is a partial scene, missing the root distribution,
    # the process definition, and the observed data.
    scene = {
            "node_count" : 12,
            "process_count" : 1,
            "state_space_shape" : [20],
            "tree" : {
                "row_nodes" : [
                    0, 7, 7, 8, 8, 9, 9, 10, 10, 11, 11],
                "column_nodes" : [
                    8, 1, 2, 7, 9, 3, 10, 6, 11, 4, 5],
                "edge_rate_scaling_factors" : [
                    0.001, 0.001, 0.001, 0.001, 0.001, 0.001,
                    0.001, 0.001, 0.001, 0.001, 0.001],
                "edge_processes" : [
                    0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0]
                }
            }

    # Add the root distribution.
    scene['root_prior'] = {
            "states" : [[i] for i in range(nstates)],
            "probabilities" : distn
            }

    # Add the process definition.
    triples = []
    for i in range(nstates):
        for j in range(nstates):
            r = rate_matrix[i, j]
            if i != j and r:
                triples.append((i, j, r))
    row_states, col_states, rates = zip(*triples)
    scene['process_definitions'] = [{
        "row_states" : [[s] for s in row_states],
        "column_states" : [[s] for s in col_states],
        "transition_rates" : rates
        }]

    # Add the observed data.
    sequences = []
    with open('mtCDNApri.aa') as fin:
        lines = fin.readlines()
        header = lines[0]
        for line in lines[1:]:
            name, sequence = line.strip().split()
            sequences.append([d[x] for x in sequence])
    columns = [list(x) for x in zip(*sequences)]
    nsites = len(columns)
    scene['observed_data'] = {
            "nodes" : [0, 1, 2, 3, 4, 5, 6],
            "variables" : [0, 0, 0, 0, 0, 0, 0],
            "iid_observations" : columns
            }

    # Update the edge rates according to a few iterations of EM.
    observation_reduction = None
    em_iterations = 6
    edge_rates = optimize_em(scene, observation_reduction, em_iterations)
    scene['tree']['edge_rate_scaling_factors'] = edge_rates

    # Report the log likelihood for the updated edge rates.
    j_in = dict(
            scene = scene,
            requests = [dict(property = 'SNNLOGL')])
    ll = process_json_in(j_in)['responses'][0]
    print(ll)


main()
-14558.5947862