[수리응용센터] Seminar on Biostatistics 일시: 2019년 7월 1일(월) 16:00~ 장소: 수리과학관 313호 발표자: 심희정 교수(University of Melbourne)
제목: riboHMM*: Comprehensive annotation of translated regions using ribosome footprint profiling data
초록: Understanding the functional effects of gene
expression critically depends on the accurate and comprehensive annotation of
sequence elements which are translated in each gene. Ribosome profiling
provides direct and genome-wide measurements of translation levels in a given
cell type. In this talk, I will first introduce a method, riboHMM, that 1)
models a codon periodicity structure in ribosome profiling data, and 2)
integrates RNA sequence information and transcript expressions to identify
translated regions in a transcript. Applying riboHMM on ribosome profiling data
collected from human lymphoblastoid cell lines, we identified 7273 novel
translated regions, including 2442 translated upstream open reading frames (uORFs) and 2551 coding sequences from
transcripts that were previously annotated as non-coding. We observed that more
than 60% of the novel coding sequences use non-canonical start codons. We also
observed that ~40% of the 2442 translated uORFs are likely to regulate the
translation of their downstream coding regions.
Motivated by this observation, I will briefly
introduce another method, riboHMM2, for annotating a comprehensive set of
translated uORFs by
jointly modelling the fine-scale structure in ribosome profiling data around
translated uORFs and
downstream coding regions. While the previous riboHMM was able to search for
translated uORFs only
in the transcripts with translated downstream coding regions, riboHMM2 enables
annotation of translated uORFs in
the entire transcripts. It also allows us to infer the regulatory impact
of uORFs on
downstream coding regions (e.g., suppression), which is useful for gene
regulation studies to understand the mechanisms of uORF actions. |