Time to read
3 minutes
Read so far

Algorithm improves speed and accuracy of colorectal tumour analyses

Thu, 12/05/2019 - 13:01
Posted in:

A new deep-learning algorithm can quickly and accurately analyse several types of genomic data from colorectal tumours for more accurate classification, which could help improve diagnosis and related treatment options, according to researchers from Bioinformatics Platform research group at MDC's Berlin Institute of Medical Systems Biology (BIMSB).

"Disease is much more complex than just one gene," said Altuna Akalin, bioinformatics scientist who leads the Bioinformatics Platform research group at BIMSB. "To appreciate the complexity, we have to use some kind of machine learning to really make use of all the data."

Colorectal tumours are extremely varied in how they develop, require different drugs and have very different survival rates. Often, they are classified into subtypes based on analysis of gene expression levels.

In the study, ‘Evaluation of colorectal cancer subtypes and cell lines using deep learning’, published in the journal Life Science Alliance, Akalin with PhD student Jonathan Ronen, wanted to look at the numerous features contained in genetic material, including gene expression, single point mutations and DNA copy-numbers, and designed the Multi-omics Autoencoder Integration platform (MAUI).

Supervised machine learning typically requires human experts to label data and then train an algorithm to predict those labels. For example, to predict eye colour from pictures of eyes, the researchers first feed the algorithm with pictures where eye colour is labelled. The algorithm learns to identify different eye colours and can independently analyse new data.

In contrast, unsupervised machine learning does not involve training. A deep-learning algorithm is fed data without labels and sifts through it to find common patterns or representative features, which are called latent factors. For example, this kind of algorithm can process pictures of faces that are not labelled in any way, then identify key features like eye colours, eyebrow shapes, nose shapes and smiles.

As a deep-learning platform, MAUI is able to analyse multiple "omics" datasets and identify the most relevant patterns or features, in this case, gene sets or pathways to colorectal cancer.

MAUI identified patterns associated with the four established subtypes of colorectal cancer, assigning tumours to subtypes with high accuracy. It also made an interesting discovery. The platform found a pattern that suggests one subtype (CMS2) might need to be split into two separate groups. The tumours have different mechanisms and survival rates. The team suggests further investigation to verify if the subtype is unique or perhaps representative of the tumour spreading. Still, it demonstrates the power of the platform to take all the data, rather than only the known genes associated with a disease and produce deeper insights.

"Data science can handle complex data that is hard to handle other ways and makes sense of it," explained Akalin. "You can feed it everything you have on the tumours and it finds meaningful patterns."

 The program was not just more accurate, it also works much faster than other machine-learning algorithms - three minutes to pick out 100 patterns compared to the other programs, which took 20 minutes and 11 hours.

"It is able to learn orders of magnitude more latent factors, at a fraction of the computation time," said Jonathan Ronen, first author of the research.

The team was surprised at how fast the system performs, especially because they did not have to use GPUs to speed up calculations. This shows how extremely well optimized the algorithm is, though they are continuing to fine-tune the system.

Jonathan Ronen and Altuna Akalin discuss the research results (Credit: Felix Petermann, MDC)
Jonathan Ronen and Altuna Akalin discuss the research results (Credit: Felix Petermann, MDC)

The team, which also included Bayer AG computational biologist Sikander Hayat, adapted their program to analyse cell lines taken from tumours and grown in labs for researching the effects of potential drug treatments. However, cell lines differ on the molecular level from real tumours in many ways. The team used MAUI to compare cell lines currently used for testing colorectal cancer drugs to see how closely they were related to real tumours. Nearly half of the lines were found to be more related to other cell lines than actual tumours. A handful were found to be the best lines most closely representing the different classes of CRC tumours.

While drug discovery research is moving away from cell lines, this insight could help maximize the potential impact of cell line research and could be adapted for other types of genetic-based drug testing tools.

Now that the deep-learning platform for colorectal cancer has been established, it could be used to analyse data for new patients.

"Think of this like a search engine," added Akalin.

A clinician could input the new patient's genetic data into MAUI to find the closest match to quickly and accurately classify the tumour. The platform could advise what drugs have been used on the closest matching tumours and how well they worked, thus helping to predict drug responses and survival outlook.

For now, this could take place in a research setting only after doctors have tried the established protocols. It is a long road for a test or system to be approved for clinical use, Akalin explained. The team is exploring the potential for commercialization with the help of the Berlin Institute of Health's Digital Health Accelerator Program. They are also in the process of adapting MAUI for other types of cancers.

To access this paper, please click here