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  1. Free, publicly-accessible full text available January 1, 2025
  2. Abstract The multiple-try Metropolis method is an interesting extension of the classical Metropolis–Hastings algorithm. However, theoretical understanding about its usefulness and convergence behavior is still lacking. We here derive the exact convergence rate for the multiple-try Metropolis Independent sampler (MTM-IS) via an explicit eigen analysis. As a by-product, we prove that an naive application of the MTM-IS is less efficient than using the simpler approach of “thinned” independent Metropolis–Hastings method at the same computational cost. We further explore more variants and find it possible to design more efficient algorithms by applying MTM to part of the target distribution or creating correlated multiple trials. 
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    Free, publicly-accessible full text available August 1, 2024
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  5. Free, publicly-accessible full text available July 3, 2024
  6. Free, publicly-accessible full text available July 3, 2024
  7. Abstract

    N6-methyladenosine (m6A) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes m6A on caRNAs. RBFOX2 can recruit RBM15, an MTC component, to facilitate methylation of promoter-associated RNAs. RBM15 also physically interacts with YTHDC1 and recruits polycomb repressive complex 2 (PRC2) to the RBFOX2-bound loci for chromatin silencing and transcription suppression. Furthermore, we found that this RBFOX2/m6A/RBM15/YTHDC1/PRC2 axis plays a critical role in myeloid leukaemia. Downregulation of RBFOX2 notably inhibits survival/proliferation of acute myeloid leukaemia cells and promotes their myeloid differentiation. RBFOX2 is also required for self-renewal of leukaemia stem/initiation cells and acute myeloid leukaemia maintenance. Our study presents a pathway of m6A MTC recruitment and m6A deposition on caRNAs, resulting in locus-selective chromatin regulation, which has potential therapeutic implications in leukaemia.

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  8. Free, publicly-accessible full text available January 1, 2024