Predicting functional variants in enhancer and promoter elements using RegulomeDB

Here we present a computational model, Score of Unified Regulatory Features (SURF), that predicts functional variants in enhancer and promoter elements. SURF is trained on data from massively parallel reporter assays and predicts the effect of variants on reporter expression levels. It achieved the top performance in the Fifth Critical Assessment of Genome Interpretation “Regulation Saturation” challenge. We also show that features queried through RegulomeDB, which are direct annotations from functional genomics data, help improve prediction accuracy beyond transfer learning features from DNA sequence‐based deep learning models. Some of the most important features include DNase footprints, especially when coupled with complementary ChIP‐seq data. Furthermore, we found our model achieved good performance in predicting allele‐specific transcription factor binding events. As an extension to the current scoring system in RegulomeDB, we expect our computational model to prioritize variants in regulatory regions, thus help the understanding of functional variants in noncoding regions that lead to disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151875/1/humu23791-sup-0001-Supp_Mat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151875/2/humu23791.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151875/3/humu23791_am.pd

CREDITORS’ RIGHTS IN PROPERTY SUBJECT TO A BENEFICIARY’S RIGHT OF WITHDRAWAL

Estate plans often give trust beneficiaries powers of withdrawal for both tax and nontax reasons. For tax reasons, these powers of withdrawal are typically limited, such as a “five or five power” or a so-called Crummey power commonly pegged to the annual gift tax exclusion amount. A central issue with limited powers of with-drawal is the right of a beneficiary’s creditor to reach trust property subject to the beneficiary’s power to withdraw. Recent uniform statutes, such as the Uniform Trust Code and the Uniform Power of Appointment Act, as well as the Restatement (Third) of Trusts, provide guidance. This Article discusses the typical reasons for creating powers of withdrawal and the historical and recent treatment of the rights of creditors of trust beneficiaries with powers of withdrawal, along with some planning considerations