Sci Simple

New Science Research Articles Everyday

# Biology # Systems Biology

EAGLE: A New Tool for Gene Expression Prediction

EAGLE predicts gene behavior across fungi, advancing biotechnology applications.

Laura Weinstock, Jenna Schambach, Anna Fisher, Cameron Kunstadt, Ethan Lee, Elizabeth Koning, William Morrell, Wittney Mays, Warren Davis, Raga Krishnakumar

― 7 min read


EAGLE Transforms Gene EAGLE Transforms Gene Prediction effectively. New model predicts fungal gene behavior
Table of Contents

In the realm of biology, understanding how genes express themselves is much like figuring out a recipe. Every ingredient must be measured just right, and if you happen to spill in that extra pinch of salt, well, dinner might not turn out as planned. Scientists have been striving for precise control over Gene Expression to optimize biological processes. This need is especially vital for things like treating diseases or making useful products from living organisms, such as fungi.

Why Gene Expression Matters

Gene expression is a crucial process in all life forms. It determines how cells function and respond to their environment. Think of it as the playbook for how an organism operates. If a gene is "switched on," it produces proteins, which are the tools of the cell. If it's "switched off," the proteins don't get made. This is essential for everything from how we grow to how we react to stress or disease.

In recent years, researchers have focused on ways to control gene expression specifically. They want to ensure that the right genes are active at the right times and in the right amounts. This tightening of the controls can lead to more efficient production of certain compounds and reduce waste.

The Role of Epigenetics

Enter epigenetics, which looks at how genes are expressed without changing the actual DNA sequence. It's a bit like having the same ingredients for a dish but preparing it in different ways. In this case, epigenetics involves various chemical modifications to DNA and proteins associated with DNA. These modifications can affect how tightly or loosely DNA is packed, which in turn influences whether genes can be accessed and used.

These chemical tweaks are stable and can sometimes even be passed down to future generations—like the family recipe that gets passed from grandma to grandkids. The key point is that these modifications can have a massive impact on how genes function.

Why Fungi?

Fungi might not be the first organism that comes to mind when you think about high-tech solutions, but these little guys are surprisingly versatile. They are like the Swiss Army knives of the biological world. Fungi can produce drugs, biofuels, and even food. They can also break down materials, making them invaluable for cleaning up the environment.

Researchers see a lot of potential in engineering fungi to not only perform specific tasks but to do them better. By tweaking their genetic controls and modifying their behavior, scientists hope to create fungal strains that are more efficient at producing useful compounds.

The Challenge of Predicting Gene Expression

One of the biggest hurdles in this research area is that different species of fungi can behave quite differently when it comes to gene expression. While the general rules are the same, the details can vary significantly. Researchers have been trying to see if the knowledge gained from one species can help understand another.

This is where EAGLE, or Evolutionary distance-Adaptable Gene expression Learned from Epigenomics, comes into play. It's not a new superhero but rather a smart framework that helps predict how genes might express themselves based on epigenetic data.

How EAGLE Works

EAGLE is like the GPS of gene prediction. It helps researchers know where to go by taking into account all the previous places they've been. It uses a mix of techniques, including Machine Learning, to analyze epigenetic modifications and make predictions about gene activity across different fungal species.

Imagine if you’ve been to a new restaurant and you remember what you ordered. You might be able to guess what you’d like next time based on past experiences. EAGLE does something similar but with genes. It takes past gene expression data from one species and applies it to another, even if they’re not closely related.

The Importance of Data

Of course, like any tool, EAGLE is only as good as the data fed into it. Researchers have gathered gene expression and epigenetic modification datasets from various fungal species. They focused on those with reliable data, ensuring the information was of high quality.

In the world of machine learning, data is everything. If you feed a model with poor information, it’s likely to make poor predictions. That’s like trying to bake a cake without a proper recipe—you might end up with something that resembles dessert, but probably not what you were hoping for.

Different Fungal Species in the Study

The researchers looked at four different species of fungi to train and test EAGLE: Neurospora crassa, Fusarium graminearum, Leptosphaeria maculans, and Aspergillus nidulans. Each of these has unique characteristics and functions, making them perfect candidates for a diverse research palette.

While these fungi are all part of the same family, they're far enough apart on the evolutionary tree to present a significant challenge. But that’s what makes the investigation exciting! It’s like venturing out of your neighborhood and exploring a whole new city.

A Peek Inside the Model

So how does EAGLE predict gene expression? It uses a mix of deep learning techniques that are designed to grasp the complex relationships between epigenetic markers and gene expression. Think of it like a talented chef trying to figure out the best way to combine flavors.

The model analyzes the presence of certain epigenetic modifications near genes and evaluates their impact on gene expression. It looks at various features and tries to make sense of how they all fit together, almost like piecing together a puzzle—except in this case, the pieces are tiny markers on a giant DNA strand.

The Results

Researchers found that EAGLE performed well on tasks where they predicted gene expression within a species. However, the model really shined when they tested it across species. The ability to predict how genes behaved in one type of Fungus using the data from another species was quite impressive.

EAGLE outperformed other models that had been benchmarked, showcasing its ability to extract important features from complex epigenetic data. This indicates a solid level of understanding of how gene expression works on a broader scale, despite the challenges posed by evolutionary differences.

Pulling Back the Curtain

To figure out what makes EAGLE tick, scientists conducted an explainability analysis. This means they looked at which factors were most influential in their predictions. By doing this, they could better understand how EAGLE arrived at its conclusions and whether they made sense from a biological standpoint.

Imagine asking a chef why they added a specific ingredient to a dish. The answer can shed light on their culinary choices, which can help you whip up a similar masterpiece in your own kitchen. This is what the analysis aimed to achieve—understanding what makes EAGLE's predictions tick.

The Future of EAGLE

With EAGLE successfully predicting gene expression across different fungal species, researchers are excited about the potential applications. This could lead to new ways of engineering fungi for various industrial purposes or even for medicinal uses.

However, the researchers are aware that this is just the beginning. There’s room for improvement in data collection, model training, and the incorporation of newer technologies. As they gather more data from various fungi, EAGLE's predictions could become even more accurate and applicable.

Conclusion

In the world of gene expression prediction, EAGLE shines as a versatile tool. Just like a Swiss Army knife for fungi, it offers a means to understand and improve gene activity across different species.

While there’s much to learn, the journey into the depths of fungal genomics promises exciting discoveries. As researchers continue to refine EAGLE, who knows what groundbreaking applications await? Perhaps the next big thing in medicine or sustainable manufacturing could come from a friendly neighborhood fungus!

And while it might sound a bit serious, the world of science is full of discoveries that can be just as surprising as a fungus that can both clean up the environment and make your favorite beer! You never know what you might find when you look closely at the tiny heroes of the biological kingdom.

Original Source

Title: A hybrid machine learning model for predicting gene expression from epigenetics across fungal species

Abstract: Understanding and controlling gene expression in organisms is essential for optimizing biological processes, whether in service of bioeconomic processes, human health, or environmental regulation. Epigenetic modifications play a significant role in regulating gene expression by altering chromatin structure, DNA accessibility and protein binding. While a significant amount is known about the combinatorial effects of epigenetics on gene expression, our understanding of the degree to which the orchestration of these mechanisms is conserved in gene expression regulation across species, particularly for non-model organisms, remains limited. In this study, we aim to predict gene expression levels based on epigenetic modifications in chromatin across different fungal species, to enable transferring information about well characterized species to poorly understood species. We developed a custom hybrid deep learning model, EAGLE (Evolutionary distance-Adaptable Gene expression Learned from Epigenomics), which combines convolutional layers and multi-head attention mechanisms to capture both local and global dependencies in epigenetic data. We demonstrate the cross-species performance of EAGLE across fungi, a kingdom containing both pathogens and biomanufacturing chassis and where understanding epigenetic regulation in under-characterized species would be transformative for bioeconomic, environmental, and biomedical applications. EAGLE outperformed shallow learning models and a modified transformer benchmarking model, achieving up to 80% accuracy and 89% AUROC for intra-species validation and 77% accuracy and 83% AUROC in cross-species prediction tasks. SHAP analysis revealed that EAGLE identifies important epigenetic features that drive gene expression, providing insights for experimental design and potential future epigenome engineering work. Our findings demonstrate the potential of EAGLE to generalize across fungal species, offering a versatile tool for optimizing fungal gene expression in multiple sectors. In addition, our architecture can be adapted for cross-species tasks across the tree of life where detailed molecular and genetic information can be scarce.

Authors: Laura Weinstock, Jenna Schambach, Anna Fisher, Cameron Kunstadt, Ethan Lee, Elizabeth Koning, William Morrell, Wittney Mays, Warren Davis, Raga Krishnakumar

Last Update: 2024-12-13 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.12.628183

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.12.628183.full.pdf

Licence: https://creativecommons.org/licenses/by-nc/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

Similar Articles