With the advent of high-throughput technologies, molecular biology is experiencing a surge in both growth and scope. As the amount of experimental data increases, the demand for the development of ways to analyze these results also increases. For example, the next-generation sequencing (NGS) technology has generated various sequencing data. Mass spectrometry- (MS-) based experiments are also widely applied in proteomics studies. Rapidly advancing technologies have offered us the opportunities to examine the genome, transcriptome, and proteome in comprehensive ways. Yet, extracting meaningful information from this vast sea of data and approaching biological problems from systems biology perspective have become the Holy Grail in bioinformatics. The main focus of this special issue is novelty: new ideas, original research findings, and practical applications that intend to answer biological questions through high-throughput technologies. The papers in this special issue present methods and experiments that demonstrate novel platforms and systems and new bioinformatics tools and models, as well as new data-analytical methods for high-throughput biological data.