Cortexa: A Resource for Brain Research

Transcriptional regulation is important for the development and functioning of the brain in mammals, both during growth and in adulthood. This involves how genes are expressed and how their RNA can be altered in different ways, especially during brain development.

#Gene Expression and Its Importance

Gene expression refers to how genes make proteins needed for brain cells to function. This is a major focus in studying brain development, how different brain cells are identified, and how diseases can change gene activity. However, comparing findings from different studies can be tricky because there can be batch effects. These are differences that come from the way the studies were done, like the type of technology used or the way the data was processed, rather than actual biological differences.

#Alternative Splicing and Its Role

Alternative splicing is a process that allows a single gene to produce different RNA versions, resulting in various proteins. This greatly increases the number of different proteins that can be created from the same gene. In the brain, alternative splicing is crucial during the development of the cortex and helps define and keep the identities of different types of brain cells. It also plays an important role in regulating gene expression by causing certain RNA to be degraded when specific conditions are met.

#Challenges in Analyzing Alternative Splicing

Even though there are many good datasets on alternative splicing in mouse brains that anyone can access, understanding the different types of splicing for each gene is still a challenge. Combining data from several sources also requires a consistent method to make sure the results can be compared meaningfully. Many existing resources focus primarily on gene expression and do not provide the ability to analyze custom data for specific types of splicing or developmental changes.

#Introducing Cortexa

To address these challenges, a new data portal called Cortexa has been created. This platform provides access to a wide range of high-quality datasets related to transcriptomic data from the neocortex and hippocampus of mice. It analyzes both gene expression and alternative splicing. A standardized analysis process has been set up to reduce batch effects between different studies. Cortexa allows scientists to easily interpret and visualize the patterns of gene expression and alternative splicing for specific genes.

#Features of Cortexa

Cortexa includes a tool known as SplicePCA, which performs a type of analysis to identify splicing patterns related to developmental changes or differences among cell types. All datasets are available for free download, making it easy for researchers to integrate them into their own work.

#Data Analysis Process

To gather the necessary data, researchers used RNA Sequencing, a method that allows for detailed analysis of RNA. They focused on specific datasets with good quality that contained information about the mouse brain. The sequencing process produced long reads of RNA, which were then processed to align with a reference genome and count gene expression levels.

Alternative splicing was detected using well-established tools, which identified different types of splicing events. The results were then visualized in ways that make them easy to understand, such as heatmaps for gene expression and sashimi plots for splicing events.

#User-Friendly Web Application

Cortexa is designed to be user-friendly. The web application offers intuitive navigation and clear visualizations, allowing a wide range of users to explore gene expression and alternative splicing patterns. Users can analyze not only the provided datasets but also their own data, using the SplicePCA tool to gain insights into their research.

#Example Use Case for SplicePCA

To show how SplicePCA works, researchers analyzed data from mice lacking a specific gene (Nova2) and compared it to normal mice. They performed standard quality checks and analysis steps to prepare the data, and then they examined the splicing events related to development and specific cell types.

By using SplicePCA, they found significant differences between the knockout samples and the normal samples. This highlighted how important the NOVA2 protein is for proper brain development, specifically in regulating splicing that impacts neuronal migration. Such findings demonstrate the value of SplicePCA in providing insights into the role of genes in brain development.

#The Importance of Alternative Splicing in the Brain

Alternative splicing is very common in the brain and plays a key role in both development and the ongoing function of different types of brain cells. In mice, there are approximately 22,000 protein-coding genes, and almost all of them undergo alternative splicing. However, the effects of many of these splicing events are not yet well understood.

Cortexa provides an easy way for researchers to access alternative splicing data for specific genes while considering developmental stages and types of brain cells. This can help them formulate hypotheses and investigate how gene expression and splicing relate to various biological processes.

#Power of Principal Component Analysis

Principal component analysis, or PCA, is a useful method for summarizing changes in splicing across different conditions. With SplicePCA, users can choose specific genes, combine their data, and compare it with normal splicing patterns seen during brain development or in various types of cells. This feature highlights the relevance of using large datasets in combination with new research findings to enrich our understanding of brain biology.

#Reducing Computational Barriers

Cortexa allows researchers to use publicly available data without the need for extensive re-analysis, which can be time-consuming and require significant computing power. By making it simple to access and analyze high-quality transcriptomic data, Cortexa opens up opportunities for a wide range of scientists, including those who may not have a strong background in computational methods.

#Conclusion

In summary, Cortexa is a valuable resource for researchers interested in gene expression and alternative splicing in the mouse brain. It provides high-quality datasets and user-friendly tools for both novice and experienced scientists. With SplicePCA, researchers can gain deeper insights into how genes regulate splicing and how this process affects brain development and function. Overall, Cortexa helps make complex biological data more accessible and easier to interpret, paving the way for new discoveries in neuroscience.