bdext 0.1.64__tar.gz → 0.1.66__tar.gz

bdext-0.1.66/PKG-INFO

@@ -0,0 +1,229 @@
+Metadata-Version: 2.1
+Name: bdext
+Version: 0.1.66
+Summary: Estimation of BDEISS-CT parameters from phylogenetic trees.
+Home-page: https://github.com/modpath/bdeissct
+Author: Anna Zhukova
+Author-email: anna.zhukova@pasteur.fr
+License: UNKNOWN
+Description: # bdext
+        
+        The bdext package provides scripts to train and assess
+        Deep-Learning-enables estimators of BD(EI)(SS)(CT) model parameters from phylogenetic trees 
+        
+        
+        
+        [//]: # ([![DOI:10.1093/sysbio/syad059](https://zenodo.org/badge/DOI/10.1093/sysbio/syad059.svg)](https://doi.org/10.1093/sysbio/syad059))
+        [//]: # ([![GitHub release](https://img.shields.io/github/v/release/evolbioinfo/bdext.svg)](https://github.com/evolbioinfo/bdext/releases))
+        [![PyPI version](https://badge.fury.io/py/bdext.svg)](https://pypi.org/project/bdext/)
+        [![PyPI downloads](https://shields.io/pypi/dm/bdext)](https://pypi.org/project/bdext)
+        [![Docker pulls](https://img.shields.io/docker/pulls/evolbioinfo/bdext)](https://hub.docker.com/r/evolbioinfo/bdext/tags)
+        
+        ## BDEISS-CT model
+        
+        The Birth-Death (BD) Exposed-Infectious (EI) with SuperSpreading (SS) and Contact-Tracing (CT) model (BDEISS-CT) 
+        can be described with the following 8 parameters:
+        
+        * average reproduction number R;
+        * average total infection duration d;
+        * incubation period d<sub>inc</sub>;
+        * sampling probability ρ;
+        * fraction of superspreaders f<sub>S</sub>;
+        * super-spreading transmission increase X<sub>S</sub>;
+        * contact tracing probability υ;
+        * contact-traced removal speed up X<sub>C</sub>.
+        
+        Setting d<sub>inc</sub>=0 removes incubation (EI), setting f<sub>S</sub>=0 removes superspreading (SS), while setting υ=0 removes contact-tracing (CT).
+        
+        For identifiability, we require the sampling probability ρ to be given by the user. 
+        The other parameters are estimated from a time-scaled phylogenetic tree.
+        
+        [//]: # (## BDEISS-CT parameter estimator)
+        
+        [//]: # ()
+        [//]: # (The bdeissct_dl package provides deep-learning-based BDEISS-CT model parameter estimator )
+        
+        [//]: # (from a user-supplied time-scaled phylogenetic tree. )
+        
+        [//]: # (User must also provide a value for one of the three BD model parameters &#40;λ, ψ, or ρ&#41;. )
+        
+        [//]: # (We recommend providing the sampling probability ρ, )
+        
+        [//]: # (which could be estimated as the number of tree tips divided by the number of declared cases for the same time period.)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # (## Input data)
+        
+        [//]: # (One needs to supply a time-scaled phylogenetic tree in newick format. )
+        
+        [//]: # (In the examples below we will use an HIV tree reconstructed from 200 sequences, )
+        
+        [//]: # (published in [[Rasmussen _et al._ PLoS Comput. Biol. 2017]]&#40;https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005448&#41;, )
+        
+        [//]: # (which you can find at [PairTree GitHub]&#40;https://github.com/davidrasm/PairTree&#41; )
+        
+        [//]: # (and in [hiv_zurich/Zurich.nwk]&#40;hiv_zurich/Zurich.nwk&#41;. )
+        
+        [//]: # ()
+        [//]: # (## Installation)
+        
+        [//]: # ()
+        [//]: # (There are 4 alternative ways to run __bdeissct_dl__ on your computer: )
+        
+        [//]: # (with [docker]&#40;https://www.docker.com/community-edition&#41;, )
+        
+        [//]: # ([apptainer]&#40;https://apptainer.org/&#41;,)
+        
+        [//]: # (in Python3, or via command line &#40;requires installation with Python3&#41;.)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # ()
+        [//]: # (### Run in python3 or command-line &#40;for linux systems, recommended Ubuntu 21 or newer versions&#41;)
+        
+        [//]: # ()
+        [//]: # (You could either install python &#40;version 3.9 or higher&#41; system-wide and then install bdeissct_dl via pip:)
+        
+        [//]: # (```bash)
+        
+        [//]: # (sudo apt install -y python3 python3-pip python3-setuptools python3-distutils)
+        
+        [//]: # (pip3 install bdeissct_dl)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # (or alternatively, you could install python &#40;version 3.9 or higher&#41; and bdeissct_dl via [conda]&#40;https://conda.io/docs/&#41; &#40;make sure that conda is installed first&#41;. )
+        
+        [//]: # (Here we will create a conda environment called _phyloenv_:)
+        
+        [//]: # (```bash)
+        
+        [//]: # (conda create --name phyloenv python=3.12)
+        
+        [//]: # (conda activate phyloenv)
+        
+        [//]: # (pip install bdeissct_dl)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # (#### Basic usage in a command line)
+        
+        [//]: # (If you installed __bdeissct_dl__ in a conda environment &#40;here named _phyloenv_&#41;, do not forget to first activate it, e.g.)
+        
+        [//]: # ()
+        [//]: # (```bash)
+        
+        [//]: # (conda activate phyloenv)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # (Run the following command to estimate the BDEISS_CT parameters and their 95% CIs for this tree, assuming the sampling probability of 0.25, )
+        
+        [//]: # (and save the estimated parameters to a comma-separated file estimates.csv.)
+        
+        [//]: # (```bash)
+        
+        [//]: # (bdeissct_infer --nwk Zurich.nwk --ci --p 0.25 --log estimates.csv)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # (#### Help)
+        
+        [//]: # ()
+        [//]: # (To see detailed options, run:)
+        
+        [//]: # (```bash)
+        
+        [//]: # (bdeissct_infer --help)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # (### Run with docker)
+        
+        [//]: # ()
+        [//]: # (#### Basic usage)
+        
+        [//]: # (Once [docker]&#40;https://www.docker.com/community-edition&#41; is installed, )
+        
+        [//]: # (run the following command to estimate BDEISS-CT model parameters:)
+        
+        [//]: # (```bash)
+        
+        [//]: # (docker run -v <path_to_the_folder_containing_the_tree>:/data:rw -t evolbioinfo/bdeissct --nwk /data/Zurich.nwk --ci --p 0.25 --log /data/estimates.csv)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # (This will produce a comma-separated file estimates.csv in the <path_to_the_folder_containing_the_tree> folder,)
+        
+        [//]: # ( containing the estimated parameter values and their 95% CIs &#40;can be viewed with a text editor, Excel or Libre Office Calc&#41;.)
+        
+        [//]: # ()
+        [//]: # (#### Help)
+        
+        [//]: # ()
+        [//]: # (To see advanced options, run)
+        
+        [//]: # (```bash)
+        
+        [//]: # (docker run -t evolbioinfo/bdeissct -h)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # ()
+        [//]: # (### Run with apptainer)
+        
+        [//]: # ()
+        [//]: # (#### Basic usage)
+        
+        [//]: # (Once [apptainer]&#40;https://apptainer.org/docs/user/latest/quick_start.html#installation&#41; is installed, )
+        
+        [//]: # (run the following command to estimate BDEISS-CT model parameters &#40;from the folder where the Zurich.nwk tree is contained&#41;:)
+        
+        [//]: # ()
+        [//]: # (```bash)
+        
+        [//]: # (apptainer run docker://evolbioinfo/bdeissct --nwk Zurich.nwk --ci --p 0.25 --log estimates.csv)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # (This will produce a comma-separated file estimates.csv,)
+        
+        [//]: # ( containing the estimated parameter values and their 95% CIs &#40;can be viewed with a text editor, Excel or Libre Office Calc&#41;.)
+        
+        [//]: # ()
+        [//]: # ()
+        [//]: # (#### Help)
+        
+        [//]: # ()
+        [//]: # (To see advanced options, run)
+        
+        [//]: # (```bash)
+        
+        [//]: # (apptainer run docker://evolbioinfo/bdeissct -h)
+        
+        [//]: # (```)
+        
+        [//]: # ()
+        [//]: # ()
+        
+Keywords: phylogenetics,birth-death model,incubation,super-spreading,contact tracing
+Platform: UNKNOWN
+Classifier: Development Status :: 4 - Beta
+Classifier: Environment :: Console
+Classifier: Intended Audience :: Developers
+Classifier: Topic :: Scientific/Engineering :: Bio-Informatics
+Classifier: Topic :: Software Development
+Classifier: Topic :: Software Development :: Libraries :: Python Modules
+Description-Content-Type: text/markdown

bdext-0.1.66/README.md

@@ -0,0 +1,211 @@
+# bdext
+
+The bdext package provides scripts to train and assess
+Deep-Learning-enables estimators of BD(EI)(SS)(CT) model parameters from phylogenetic trees 
+
+
+
+[//]: # ([![DOI:10.1093/sysbio/syad059](https://zenodo.org/badge/DOI/10.1093/sysbio/syad059.svg)](https://doi.org/10.1093/sysbio/syad059))
+[//]: # ([![GitHub release](https://img.shields.io/github/v/release/evolbioinfo/bdext.svg)](https://github.com/evolbioinfo/bdext/releases))
+[![PyPI version](https://badge.fury.io/py/bdext.svg)](https://pypi.org/project/bdext/)
+[![PyPI downloads](https://shields.io/pypi/dm/bdext)](https://pypi.org/project/bdext)
+[![Docker pulls](https://img.shields.io/docker/pulls/evolbioinfo/bdext)](https://hub.docker.com/r/evolbioinfo/bdext/tags)
+
+## BDEISS-CT model
+
+The Birth-Death (BD) Exposed-Infectious (EI) with SuperSpreading (SS) and Contact-Tracing (CT) model (BDEISS-CT) 
+can be described with the following 8 parameters:
+
+* average reproduction number R;
+* average total infection duration d;
+* incubation period d<sub>inc</sub>;
+* sampling probability ρ;
+* fraction of superspreaders f<sub>S</sub>;
+* super-spreading transmission increase X<sub>S</sub>;
+* contact tracing probability υ;
+* contact-traced removal speed up X<sub>C</sub>.
+
+Setting d<sub>inc</sub>=0 removes incubation (EI), setting f<sub>S</sub>=0 removes superspreading (SS), while setting υ=0 removes contact-tracing (CT).
+
+For identifiability, we require the sampling probability ρ to be given by the user. 
+The other parameters are estimated from a time-scaled phylogenetic tree.
+
+[//]: # (## BDEISS-CT parameter estimator)
+
+[//]: # ()
+[//]: # (The bdeissct_dl package provides deep-learning-based BDEISS-CT model parameter estimator )
+
+[//]: # (from a user-supplied time-scaled phylogenetic tree. )
+
+[//]: # (User must also provide a value for one of the three BD model parameters &#40;λ, ψ, or ρ&#41;. )
+
+[//]: # (We recommend providing the sampling probability ρ, )
+
+[//]: # (which could be estimated as the number of tree tips divided by the number of declared cases for the same time period.)
+
+[//]: # ()
+[//]: # ()
+[//]: # (## Input data)
+
+[//]: # (One needs to supply a time-scaled phylogenetic tree in newick format. )
+
+[//]: # (In the examples below we will use an HIV tree reconstructed from 200 sequences, )
+
+[//]: # (published in [[Rasmussen _et al._ PLoS Comput. Biol. 2017]]&#40;https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005448&#41;, )
+
+[//]: # (which you can find at [PairTree GitHub]&#40;https://github.com/davidrasm/PairTree&#41; )
+
+[//]: # (and in [hiv_zurich/Zurich.nwk]&#40;hiv_zurich/Zurich.nwk&#41;. )
+
+[//]: # ()
+[//]: # (## Installation)
+
+[//]: # ()
+[//]: # (There are 4 alternative ways to run __bdeissct_dl__ on your computer: )
+
+[//]: # (with [docker]&#40;https://www.docker.com/community-edition&#41;, )
+
+[//]: # ([apptainer]&#40;https://apptainer.org/&#41;,)
+
+[//]: # (in Python3, or via command line &#40;requires installation with Python3&#41;.)
+
+[//]: # ()
+[//]: # ()
+[//]: # ()
+[//]: # (### Run in python3 or command-line &#40;for linux systems, recommended Ubuntu 21 or newer versions&#41;)
+
+[//]: # ()
+[//]: # (You could either install python &#40;version 3.9 or higher&#41; system-wide and then install bdeissct_dl via pip:)
+
+[//]: # (```bash)
+
+[//]: # (sudo apt install -y python3 python3-pip python3-setuptools python3-distutils)
+
+[//]: # (pip3 install bdeissct_dl)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # (or alternatively, you could install python &#40;version 3.9 or higher&#41; and bdeissct_dl via [conda]&#40;https://conda.io/docs/&#41; &#40;make sure that conda is installed first&#41;. )
+
+[//]: # (Here we will create a conda environment called _phyloenv_:)
+
+[//]: # (```bash)
+
+[//]: # (conda create --name phyloenv python=3.12)
+
+[//]: # (conda activate phyloenv)
+
+[//]: # (pip install bdeissct_dl)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # ()
+[//]: # (#### Basic usage in a command line)
+
+[//]: # (If you installed __bdeissct_dl__ in a conda environment &#40;here named _phyloenv_&#41;, do not forget to first activate it, e.g.)
+
+[//]: # ()
+[//]: # (```bash)
+
+[//]: # (conda activate phyloenv)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # (Run the following command to estimate the BDEISS_CT parameters and their 95% CIs for this tree, assuming the sampling probability of 0.25, )
+
+[//]: # (and save the estimated parameters to a comma-separated file estimates.csv.)
+
+[//]: # (```bash)
+
+[//]: # (bdeissct_infer --nwk Zurich.nwk --ci --p 0.25 --log estimates.csv)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # (#### Help)
+
+[//]: # ()
+[//]: # (To see detailed options, run:)
+
+[//]: # (```bash)
+
+[//]: # (bdeissct_infer --help)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # ()
+[//]: # (### Run with docker)
+
+[//]: # ()
+[//]: # (#### Basic usage)
+
+[//]: # (Once [docker]&#40;https://www.docker.com/community-edition&#41; is installed, )
+
+[//]: # (run the following command to estimate BDEISS-CT model parameters:)
+
+[//]: # (```bash)
+
+[//]: # (docker run -v <path_to_the_folder_containing_the_tree>:/data:rw -t evolbioinfo/bdeissct --nwk /data/Zurich.nwk --ci --p 0.25 --log /data/estimates.csv)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # (This will produce a comma-separated file estimates.csv in the <path_to_the_folder_containing_the_tree> folder,)
+
+[//]: # ( containing the estimated parameter values and their 95% CIs &#40;can be viewed with a text editor, Excel or Libre Office Calc&#41;.)
+
+[//]: # ()
+[//]: # (#### Help)
+
+[//]: # ()
+[//]: # (To see advanced options, run)
+
+[//]: # (```bash)
+
+[//]: # (docker run -t evolbioinfo/bdeissct -h)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # ()
+[//]: # ()
+[//]: # (### Run with apptainer)
+
+[//]: # ()
+[//]: # (#### Basic usage)
+
+[//]: # (Once [apptainer]&#40;https://apptainer.org/docs/user/latest/quick_start.html#installation&#41; is installed, )
+
+[//]: # (run the following command to estimate BDEISS-CT model parameters &#40;from the folder where the Zurich.nwk tree is contained&#41;:)
+
+[//]: # ()
+[//]: # (```bash)
+
+[//]: # (apptainer run docker://evolbioinfo/bdeissct --nwk Zurich.nwk --ci --p 0.25 --log estimates.csv)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # (This will produce a comma-separated file estimates.csv,)
+
+[//]: # ( containing the estimated parameter values and their 95% CIs &#40;can be viewed with a text editor, Excel or Libre Office Calc&#41;.)
+
+[//]: # ()
+[//]: # ()
+[//]: # (#### Help)
+
+[//]: # ()
+[//]: # (To see advanced options, run)
+
+[//]: # (```bash)
+
+[//]: # (apptainer run docker://evolbioinfo/bdeissct -h)
+
+[//]: # (```)
+
+[//]: # ()
+[//]: # ()

{bdext-0.1.64 → bdext-0.1.66}/bdeissct_dl/__init__.py

@@ -7,12 +7,10 @@ warnings.filterwarnings('ignore', r'divide by zero encountered in log')
 
 
 MODEL_PATH = os.path.join(os.path.dirname(__file__), 'models')
-TRAINING_PATH = os.path.join(os.path.dirname(__file__), 'data')
-
 
 
 EPOCHS = 1000
-BATCH_SIZE = 1024
+BATCH_SIZE = 8192
 
 
 

bdext-0.1.66/bdeissct_dl/bdeissct_model.py

@@ -0,0 +1,78 @@
+from collections import defaultdict
+
+LA = 'la'
+PSI = 'psi'
+RHO = 'rho'
+INFECTIOUS_TIME = 'd_I'
+REPRODUCTIVE_NUMBER = 'R'
+INFECTION_DURATION = 'd'
+
+MU = 'mu'
+INCUBATION_PERIOD = 'd_E'
+
+F_S = 'f_S'
+X_S = 'X_S'
+
+
+X_C = 'X_C'
+UPSILON = 'upsilon'
+
+KAPPA = 'kappa'
+REMOVAL_TIME_AFTER_NOTIFICATION = 'd_C'
+
+RATE_PARAMETERS = (LA, PSI, MU)
+TIME_PARAMETERS = (INCUBATION_PERIOD, INFECTIOUS_TIME, REMOVAL_TIME_AFTER_NOTIFICATION, INFECTION_DURATION)
+
+
+
+DEFAULT_MIN_PROB = 1e-6
+DEFAULT_MAX_PROB = 1
+DEFAULT_MIN_RATE = 1e-3
+DEFAULT_MAX_RATE = 1e3
+
+
+BD = 'BD'
+BDCT = 'BDCT'
+
+BDEI = 'BDEI'
+BDEICT = 'BDEICT'
+
+BDSS = 'BDSS'
+BDSSCT = 'BDSSCT'
+
+BDEISS = 'BDEISS'
+BDEISSCT = 'BDEISSCT'
+
+
+
+MODEL_FINDER = 'MF'
+
+MODELS = (BD, BDCT, \
+          BDEI, BDEICT, \
+          BDSS, BDSSCT, \
+          BDEISS, BDEISSCT)
+
+
+TARGET_CT_COLUMNS = (UPSILON, X_C)
+TARGET_INCUBATION_COLUMNS = (INCUBATION_PERIOD,)
+TARGET_SS_COLUMNS = (F_S, X_S)
+TARGET_COLUMNS_BD = (REPRODUCTIVE_NUMBER, INFECTION_DURATION)
+TARGET_COLUMNS_BDCT = TARGET_COLUMNS_BD + TARGET_CT_COLUMNS
+TARGET_COLUMNS_BDEI = TARGET_COLUMNS_BD + TARGET_INCUBATION_COLUMNS
+TARGET_COLUMNS_BDEICT = TARGET_COLUMNS_BDEI + TARGET_CT_COLUMNS
+TARGET_COLUMNS_BDSS = TARGET_COLUMNS_BD + TARGET_SS_COLUMNS
+TARGET_COLUMNS_BDSSCT = TARGET_COLUMNS_BDSS + TARGET_CT_COLUMNS
+TARGET_COLUMNS_BDEISS = TARGET_COLUMNS_BDEI + TARGET_SS_COLUMNS
+TARGET_COLUMNS_BDEISSCT = TARGET_COLUMNS_BDEISS + TARGET_CT_COLUMNS
+
+
+MODEL2TARGET_COLUMNS = defaultdict(lambda: TARGET_COLUMNS_BDEISSCT)
+MODEL2TARGET_COLUMNS.update({BD: TARGET_COLUMNS_BD,
+                             BDEI: TARGET_COLUMNS_BDEI,
+                             BDSS: TARGET_COLUMNS_BDSS,
+                             BDEISS: TARGET_COLUMNS_BDEISS,
+                             BDCT: TARGET_COLUMNS_BDCT,
+                             BDEICT: TARGET_COLUMNS_BDEICT,
+                             BDSSCT: TARGET_COLUMNS_BDSSCT,
+                             BDEISSCT: TARGET_COLUMNS_BDEISSCT
+                             })

bdext-0.1.66/bdeissct_dl/dl_model.py

@@ -0,0 +1,89 @@
+import tensorflow as tf
+from tensorflow.python.keras.utils.generic_utils import register_keras_serializable
+
+from bdeissct_dl.bdeissct_model import F_S, UPSILON, REPRODUCTIVE_NUMBER, \
+    INFECTION_DURATION, X_S, X_C, RHO, INCUBATION_PERIOD
+
+LEARNING_RATE = 0.001
+
+LOSS_WEIGHTS = {
+    REPRODUCTIVE_NUMBER: 1,
+    INFECTION_DURATION: 1,
+    INCUBATION_PERIOD: 1,
+    F_S: 200, # as it is a value between 0 and 0.5, we multiply by 200 to scale it to [0, 100]
+    UPSILON: 100,
+    X_C: 1,
+    X_S: 1
+}
+
+@register_keras_serializable(package="bdeissct_dl", name="half_sigmoid")
+def half_sigmoid(x):
+    return 0.5 * tf.sigmoid(x)  # range ~ [0, 0.5)
+
+@register_keras_serializable(package="bdeissct_dl", name="relu_plus_one")
+def relu_plus_one(x):
+    return 1 + tf.nn.relu(x)  # range ~ [1, infinity)
+
+
+
+LOSS_FUNCTIONS = {
+    REPRODUCTIVE_NUMBER: "mean_absolute_percentage_error",
+    INFECTION_DURATION: "mean_absolute_percentage_error",
+    INCUBATION_PERIOD: "mean_absolute_percentage_error",
+    UPSILON: 'mae',
+    RHO: 'mean_absolute_percentage_error',
+    X_C: "mean_absolute_percentage_error",
+    F_S: 'mae',
+    X_S: "mean_absolute_percentage_error",
+}
+
+
+def build_model(target_columns, n_x, optimizer=None, metrics=None):
+    """
+    Build a FFNN of funnel shape with 4 hidden layers.
+    We use a 50% dropout after the first 2 hidden layers.
+    This architecture follows the PhyloDeep paper [Voznica et al. Nature 2022].
+
+    :param n_x: input size (number of features)
+    :param optimizer: by default Adam with learning rate of 0.001
+    :param metrics: evaluation metrics, by default no metrics
+    :return: the model instance: tf.keras.models.Sequential
+    """
+
+    inputs = tf.keras.Input(shape=(n_x,))
+
+    # (Your hidden layers go here)
+    x = tf.keras.layers.Dense(128, activation='elu', name=f'layer1_dense256_elu')(inputs)
+    x = tf.keras.layers.Dropout(0.5, name='dropout1_50')(x)
+    x = tf.keras.layers.Dense(64, activation='elu', name=f'layer2_dense128_elu')(x)
+    x = tf.keras.layers.Dropout(0.5, name='dropout2_50')(x)
+    x = tf.keras.layers.Dense(32, activation='elu', name=f'layer3_dense64elu')(x)
+    x = tf.keras.layers.Dense(16, activation='elu', name=f'layer4_dense32_elu')(x)
+
+    outputs = {}
+
+    if REPRODUCTIVE_NUMBER in target_columns:
+        outputs[REPRODUCTIVE_NUMBER] = tf.keras.layers.Dense(1, activation="softplus", name=REPRODUCTIVE_NUMBER)(x) # positive values only
+    if INFECTION_DURATION in target_columns:
+        outputs[INFECTION_DURATION] = tf.keras.layers.Dense(1, activation="softplus", name=INFECTION_DURATION)(x) # positive values only
+    if INCUBATION_PERIOD in target_columns:
+        outputs[INCUBATION_PERIOD] = tf.keras.layers.Dense(1, activation="softplus", name=INCUBATION_PERIOD)(x) # positive values only
+    if F_S in target_columns:
+        outputs[F_S] = tf.keras.layers.Dense(1, activation=half_sigmoid, name="FS_logits")(x)
+    if X_S in target_columns:
+        outputs[X_S] = tf.keras.layers.Dense(1, activation=relu_plus_one, name="XS_logits")(x)
+    if UPSILON in target_columns:
+        outputs[UPSILON] = tf.keras.layers.Dense(1, activation="sigmoid", name="ups_logits")(x)
+    if X_C in target_columns:
+        outputs[X_C] = tf.keras.layers.Dense(1, activation=relu_plus_one, name="XC_logits")(x)
+
+    model = tf.keras.models.Model(inputs=inputs, outputs=outputs)
+
+    if optimizer is None:
+        optimizer = tf.keras.optimizers.Adam(learning_rate=LEARNING_RATE)
+
+    model.compile(optimizer=optimizer,
+                  loss={col: LOSS_FUNCTIONS[col] for col in outputs.keys()},
+                  loss_weights={col: LOSS_WEIGHTS[col] for col in outputs.keys()},
+                  metrics=metrics)
+    return model