Advance articles alert 12 July 2019

1. An ensemble method for interval-censored time-to-event data
Summary
Interval-censored(区间缺失) data analysis is important in biomedical statistics for any type of time-to-event response where the time of response is not known exactly, but rather only known to occur between two assessment times. Many clinical trials and longitudinal studies（纵向研究） generate interval-censored data; one common example occurs in medical studies that entail periodic(周期的、定期的) follow-up. In this article, we propose a survival forest method for interval-censored data based on the conditional inference framework. We describe how this framework can be adapted to the situation of interval-censored data. We show that the tuning parameters have a non-negligible effect on the survival forest performance and guidance is provided on how to tune the parameters in a data-dependent way to improve the overall performance of the method. Using Monte Carlo simulations, we find that the proposed survival forest is at least as effective as a survival tree method when the underlying model has a tree structure, performs similarly to an interval-censored Cox proportional hazards model fit when the true relationship is linear, and outperforms the survival tree method and Cox model when the true relationship is nonlinear. We illustrate the application of the method on a tooth emergence data set.

2.Selection-adjusted inference: an application to confidence intervals for cis-eQTL effect sizes
Snigdha Panigrahi, Junjie Zhu, Chiara Sabatti
Biostatistics, kxz024, https://doi.org/10.1093/biostatistics/kxz024

Summary
The goal of expression quantitative trait loci (eQTL) studies is to identify the genetic variants that influence the expression levels of the genes in an organism. High throughput technology has made such studies possible: in a given tissue sample, it enables us to quantify the expression levels of approximately 20 000 genes and to record the alleles present at millions of genetic polymorphisms. While obtaining this data is relatively cheap once a specimen is at hand, obtaining human tissue remains a costly endeavor: eQTL studies continue to be based on relatively small sample sizes, with this limitation particularly serious for tissues as brain, liver, etc.—often the organs of most immediate medical relevance. Given the high-dimensional nature of these datasets and the large number of hypotheses tested, the scientific community has adopted early on multiplicity （多样性）adjustment procedures. These testing procedures primarily control the false discoveries rate for the identification of genetic variants with influence on the expression levels. In contrast, a problem that has not received much attention to date is that of providing estimates of the effect sizes associated with these variants, in a way that accounts for the considerable amount of selection. Yet, given the difficulty of procuring additional samples, this challenge is of practical importance. We illustrate in this work how the recently developed conditional inference approach can be deployed to obtain confidence intervals for the eQTL effect sizes with reliable coverage. The procedure we propose is based on a randomized hierarchical strategy （分层策略）with a 2-fold contribution: (1) it reflects the selection steps typically adopted in state of the art investigations and (2) it introduces the use of randomness instead of data-splitting to maximize the use of available data. Analysis of the GTEx Liver dataset (v6) suggests that naively obtained confidence intervals would likely not cover the true values of effect sizes and that the number of local genetic polymorphisms influencing the expression level of genes might be underestimated.（低估的）