Background and Methodology
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Goals
“RNA, not DNA, is the computational engine of the cell.” ( Revolutionary Genetics Research Shows RNA May Rule Our Genome | Scientific American 2024.7. Cover Story).
We develop bioinformatics technology on noncoding RNAs from multiple perspectives/models of RNA structure and post-transcriptional regulation (e.g., splicing and editing); and explore its practice in the precise diagnosis and treatment of complex diseases. We utilize bioinformatics based on new AI technologies and multi-omics data to explore novel targets in the form of noncoding RNA in complex diseases such as cancer and autoimmune diseases, through cooperation with front-line doctors and experts. While studying RNA regulation network, some targets can be used as biomarkers for personalized and precise diagnosis and treatment, and some targets can be used as drug targets for drug design through AI.
Background
About 20 thousand protein-coding genes in human were transcribed and tranlsated from only ~1.5% of human genome sequence. On the other hand, ~70% or more of the human genome are transcribed into RNAs. Many of them are noncoding RNAs (ncRNAs), which are not well studied yet.
“By 2020 the ENCODE project said it had identified around 37,600 noncoding genes—that is, DNA stretches with instructions for RNA molecules that do not code for proteins. That is almost twice as many as there are protein-coding genes. Other tallies vary widely, from around 18,000 to close to 96,000. … In a 2024 commentary for the journal Science, the duo described these findings as part of an RNA revolution. … they undercut the way we think our biology works. Ever since the epochal discovery about DNA’s double helix and how it encodes information, the bedrock idea of molecular biology has been that there are precisely encoded instructions that program specific molecules for particular tasks. But ncRNAs seem to point to a fuzzier, more collective, logic to life. It is a logic that is harder to discern and harder to understand. But if scientists can learn to live with the fuzziness, this view of life may turn out to be more complete.” ( Revolutionary Genetics Research Shows RNA May Rule Our Genome | Scientific American 2024.7. Cover Story)
RNA regulation in immune system. RNAs are dynamicly regulated during transcription. In addition, after RNA is transcribed, it will also have very complex and fine post-transcriptional regulation, such as alternative splicing (AS), alternative polyadenylation (APA), degradation, editing, modification, cellular localization and so on. These are closely related to the structure of RNA itself and the proteins that recognize RNA sequence and structure. At the same time, RNAs, especially noncoding RNAs (ncRNAs), also regulate other macromolecules, thus playing important roles in innate immune response to viruses and cancer immunity. We explore these complex regulatory processes in complex diseases such as cancer and autoimmune diseases, which are applied to immunotherapy.
Methods
Leveraging new AI technologies for RNA modeling (i.e., RNA-Talk models) that tokenize information at sequence and/or structure levels, we discover and decipher the various molecular interactions and biological regulatory networks mediated by RNA.
RNA Modeling