HypoClock#

Index#

  1. Instantiate model class

  2. Define clock metadata

  3. Download clock dependencies

  4. Load features

  5. Load weights into base model

  6. Load reference values

  7. Load preprocess and postprocess objects

  8. Check all clock parameters

  9. Basic test

  10. Save torch model

  11. Clear directory

Let’s first import some packages:

[1]:
import os
import inspect
import shutil
import json
import torch
import pandas as pd
import pyaging as pya

Instantiate model class#

[2]:
def print_entire_class(cls):
    source = inspect.getsource(cls)
    print(source)

print_entire_class(pya.models.HypoClock)
class HypoClock(pyagingModel):
    def __init__(self):
        super().__init__()

    def preprocess(self, x):
        """
        Compute mean beta per sample, excluding missing (-1) values.
        """
        means = []
        for row in x:
            filtered_row = row[row != -1]
            if len(filtered_row) > 0:
                mean = torch.mean(filtered_row)
            else:
                mean = torch.tensor(float("nan"), device=x.device, dtype=x.dtype)
            means.append(mean)
        return torch.vstack(means)

    def postprocess(self, x):
        return 1 - x

[3]:
model = pya.models.HypoClock()

Define clock metadata#

[4]:
model.metadata["clock_name"] = "hypoclock"
model.metadata["data_type"] = "DNA methylation"  # Paper: HypoClock is based on DNA methylation at solo-WCGW sites.
model.metadata["species"] = "Homo sapiens"  # Paper: The HypoClock analysis uses human Illumina 450K solo-WCGW probes.
model.metadata["year"] = 2020
model.metadata["approved_by_author"] = "⌛"
model.metadata["citation"] = "Teschendorff, Andrew E. \"A comparison of epigenetic mitotic-like clocks for cancer risk prediction.\" Genome Medicine 12 (2020): 56."
model.metadata["doi"] = "https://doi.org/10.1186/s13073-020-00752-3"
model.metadata["notes"] = "Pyaging returns an inverted HypoClock burden score, 1 minus the mean beta value across 678 solo-WCGW CpGs; higher values therefore indicate deeper PMD hypomethylation. The assigned 2018 paper is the biological precursor, while the named 678-site implementation is from 2020."
model.metadata["research_only"] = None
model.metadata["tissue"] = ["multi-tissue"]  # Paper: Solo-WCGW PMD hypomethylation was evaluated across diverse normal tissues, blood lineages and primary tumors.
model.metadata["predicts"] = ["mitotic age"]  # Paper: HypoClock is a mitotic-like model based on hypomethylation at solo-WCGW sites.
model.metadata["training_target"] = ["not applicable"]  # Paper: HypoClock is calculated as an average methylation score rather than fit to an outcome.
model.metadata["unit"] = ["beta value"]  # Paper: The packaged output is one minus mean methylation across the selected CpGs, retaining a methylation beta-derived scale.
model.metadata["model_type"] = "mean aggregation"  # Paper: The score is the average DNAm over selected solo-WCGW probes.
model.metadata["platform"] = ["Illumina 450K"]  # Paper: The 678-site implementation uses solo-WCGWs represented on Illumina 450K arrays.
model.metadata["population"] = "human, age unspecified"  # Paper: HypoClock was assessed across normal adult tissues, premalignant lesions and cancers.
model.metadata["journal"] = "Genome Medicine"
model.metadata["last_author"] = "Andrew E. Teschendorff"
model.metadata["n_features"] = 678
model.metadata["citations"] = 452
model.metadata["citations_date"] = "2026-07-05"

Download clock dependencies#

Download directly with curl#

[5]:
supplementary_url = "https://raw.githubusercontent.com/aet21/EpiMitClocks/master/data/dataETOC3.rda"
supplementary_file_name = "dataETOC3.rda"
os.system(f"curl -L -o {supplementary_file_name} {supplementary_url}")
  % Total    % Received % Xferd  Average Speed   Time    Time     Time  Current
                                 Dload  Upload   Total   Spent    Left  Speed
100 30851  100 30851    0     0   425k      0 --:--:-- --:--:-- --:--:--  430k
[5]:
0

Load features#

From R data#

[6]:
r_cmd = (
    "load('dataETOC3.rda'); "
    "df <- data.frame(cpg=dataETOC3.l[[4]]); "
    "write.csv(df, 'hypoclock_cpgs.csv', row.names=FALSE)"
)
os.system(f"Rscript -e \"{r_cmd}\"")

features_df = pd.read_csv('hypoclock_cpgs.csv')
model.features = features_df['cpg'].tolist()

assert len(model.features) == 678, f"Expected 678 CpGs, got {len(model.features)}"

Load weights into base model#

[8]:
weights = torch.tensor([1.0]).unsqueeze(0)
intercept = torch.tensor([0.0])

Linear model#

[9]:
base_model = pya.models.LinearModel(input_dim=1)

base_model.linear.weight.data = weights.float()
base_model.linear.bias.data = intercept.float()

model.base_model = base_model

Load reference values#

[10]:
model.reference_values = [-1]*len(model.features)

Load preprocess and postprocess objects#

[11]:
model.preprocess_name = "mean"
model.preprocess_dependencies = None
[12]:
model.postprocess_name = "one_minus"
model.postprocess_dependencies = None

Check all clock parameters#

[13]:
pya.utils.print_model_details(model)

%==================================== Model Details ====================================%
Model Attributes:

training: True
metadata: {'approved_by_author': '⌛',
 'citation': 'Zhou, Wanding, et al. "DNA methylation loss in late-replicating '
             'domains is linked to mitotic cell division." Nature Genetics 50, '
             'no. 4 (2018): 591-602.',
 'clock_name': 'hypoclock',
 'data_type': 'methylation',
 'doi': 'https://doi.org/10.1038/s41588-018-0073-4',
 'notes': 'HypoClock score is 1 - mean beta across 678 solo-WCGW CpGs; '
          'reference values are -1 to ignore missing.',
 'research_only': None,
 'species': 'Homo sapiens',
 'version': None,
 'year': 2018}
reference_values: [-1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1, -1]... [Total elements: 678]
preprocess_name: 'mean'
preprocess_dependencies: None
postprocess_name: 'one_minus'
postprocess_dependencies: None
features: ['cg01689796', 'cg17753162', 'cg26150621', 'cg11684734', 'cg05812697', 'cg24052817', 'cg01827202', 'cg12277524', 'cg06160606', 'cg12758960', 'cg12270633', 'cg25939869', 'cg16823292', 'cg17041296', 'cg17325792', 'cg05347985', 'cg04789392', 'cg16320208', 'cg01779525', 'cg08009265', 'cg08244156', 'cg14711592', 'cg16577588', 'cg03114253', 'cg02245566', 'cg22601108', 'cg01068621', 'cg21291134', 'cg20491963', 'cg07725889']... [Total elements: 678]
base_model_features: None

%==================================== Model Details ====================================%
Model Structure:

base_model: LinearModel(
  (linear): Linear(in_features=1, out_features=1, bias=True)
)

%==================================== Model Details ====================================%
Model Parameters and Weights:

base_model.linear.weight: tensor([[1.]])
base_model.linear.bias: tensor([0.])

%==================================== Model Details ====================================%

Basic test#

[14]:
torch.manual_seed(42)
input = torch.randn(10, len(model.features), dtype=float)
model.eval()
model.to(float)
pred = model(input)
pred
[14]:
tensor([[0.9638],
        [0.9622],
        [1.0423],
        [1.0675],
        [1.0330],
        [0.9733],
        [0.9686],
        [1.0028],
        [0.9955],
        [0.9212]], dtype=torch.float64, grad_fn=<RsubBackward1>)

Save torch model#

[15]:
torch.save(model, f"../weights/{model.metadata['clock_name']}.pt")

Clear directory#

[16]:
# Function to remove a folder and all its contents
def remove_folder(path):
    try:
        shutil.rmtree(path)
        print(f"Deleted folder: {path}")
    except Exception as e:
        print(f"Error deleting folder {path}: {e}")

# Get a list of all files and folders in the current directory
all_items = os.listdir('.')

# Loop through the items
for item in all_items:
    # Check if it's a file and does not end with .ipynb
    if os.path.isfile(item) and not item.endswith('.ipynb'):
        os.remove(item)
        print(f"Deleted file: {item}")
    # Check if it's a folder
    elif os.path.isdir(item):
        remove_folder(item)
Deleted file: dataETOC3.rda
Deleted file: hypoclock_cpgs.csv