Hello,

I'm interested in delving deeper into the mathematical and theoretical foundations behind methods commonly employed in bioinformatics. For example, while I understand that the limma package utilizes linear regression for differential expression analysis, I seek a comprehensive understanding of the underlying theory and rationale for employing linear regression in this context.

Many bioinformatics resources tend to focus on practical aspects such as handling data files like FASTA and FASTQ, or discussing next-generation sequencing technologies. However, I've found that few delve into the mathematical and theoretical underpinnings of the analysis methods. While some resources provide code and instructions on how to use these methods, they often lack explanations regarding the underlying principles and when one should apply them.

Can you suggest reliable resources providing thorough yet accessible explanations for beginners seeking to deepen their understanding of bioinformatics methods following completion of a biology undergraduate degree?

There is inherent contradiction in asking for

thorough yet accessible explanations for beginners. In most cases you will find a thorough explanation in original papers describing the methodology, but not sure that will be accessible enough.