Rapid advancements in collection and dissemination of multi-platform molecular and genomics data has resulted in enormous opportunities to aggregate such data in order to understand, prevent, and treat human diseases. While significant improvements have been made in multi-omic data integration methods to discover biological markers and mechanisms underlying both prognosis and treatment, the precise cellular functions governing these complex mechanisms still need detailed and data-driven de-novo evaluations. We propose a framework called Functional Integrative Bayesian Analysis of High-dimensional Multiplatform Genomic Data (fiBAG), that allows simultaneous identification of upstream functional evidence of proteogenomic biomarkers and the incorporation of such knowledge in Bayesian variable selection models to improve signal detection. fiBAG employs a conflation of Gaussian process models to quantify (possibly non-linear) functional evidence via Bayes factors, which are then mapped to a novel calibrated spike-and-slab prior, thus guiding selection and providing functional relevance to the associations with patient outcomes. Using simulations, we illustrate how integrative methods with functional calibration have higher power to detect disease related markers than non-integrative approaches. We demonstrate the profitability of fiBAG via a pan-cancer analysis of 14 cancer types to identify and assess the cellular mechanisms of proteogenomic markers associated with cancer stemness and patient survival.

我们提出了一种变分贝叶斯比例危险模型，用于预测和可变选择的关于高维存活数据。我们的方法基于平均场变分近似，克服了MCMC的高计算成本，而保留有用的特征，提供优异的点估计，并通过后夹层概念提供可变选择的自然机制。我们提出的方法的性能通过广泛的仿真进行评估，并与其他最先进的贝叶斯变量选择方法进行比较，展示了可比或更好的性能。最后，我们展示了如何在两个转录组数据集上使用所提出的方法进行审查的生存结果，其中我们识别具有预先存在的生物解释的基因。

回归模型用于各种应用，为来自不同领域的研究人员提供强大的科学工具。线性或简单的参数，模型通常不足以描述输入变量与响应之间的复杂关系。通过诸如神经网络的灵活方法可以更好地描述这种关系，但这导致不太可解释的模型和潜在的过度装备。或者，可以使用特定的参数非线性函数，但是这种功能的规范通常是复杂的。在本文中，我们介绍了一种灵活的施工方法，高度灵活的非线性参数回归模型。非线性特征是分层的，类似于深度学习，但对要考虑的可能类型的功能具有额外的灵活性。这种灵活性，与变量选择相结合，使我们能够找到一小部分重要特征，从而可以更具可解释的模型。在可能的功能的空间内，考虑了贝叶斯方法，基于它们的复杂性引入功能的前沿。采用遗传修改模式跳跃马尔可夫链蒙特卡罗算法来执行贝叶斯推理和估计模型平均的后验概率。在各种应用中，我们说明了我们的方法如何用于获得有意义的非线性模型。此外，我们将其预测性能与多个机器学习算法进行比较。

发现新药是寻求并证明因果关系。作为一种新兴方法利用人类的知识和创造力，数据和机器智能，因果推论具有减少认知偏见并改善药物发现决策的希望。尽管它已经在整个价值链中应用了，但因子推理的概念和实践对许多从业者来说仍然晦涩难懂。本文提供了有关因果推理的非技术介绍，审查了其最新应用，并讨论了在药物发现和开发中采用因果语言的机会和挑战。

预测组合在预测社区中蓬勃发展，近年来，已经成为预测研究和活动主流的一部分。现在，由单个（目标）系列产生的多个预测组合通过整合来自不同来源收集的信息，从而提高准确性，从而减轻了识别单个“最佳”预测的风险。组合方案已从没有估计的简单组合方法演变为涉及时间变化的权重，非线性组合，组件之间的相关性和交叉学习的复杂方法。它们包括结合点预测和结合概率预测。本文提供了有关预测组合的广泛文献的最新评论，并参考可用的开源软件实施。我们讨论了各种方法的潜在和局限性，并突出了这些思想如何随着时间的推移而发展。还调查了有关预测组合实用性的一些重要问题。最后，我们以当前的研究差距和未来研究的潜在见解得出结论。

在2015年和2019年之间，地平线的成员2020年资助的创新培训网络名为“Amva4newphysics”，研究了高能量物理问题的先进多变量分析方法和统计学习工具的定制和应用，并开发了完全新的。其中许多方法已成功地用于提高Cern大型Hadron撞机的地图集和CMS实验所执行的数据分析的敏感性;其他几个人，仍然在测试阶段，承诺进一步提高基本物理参数测量的精确度以及新现象的搜索范围。在本文中，在研究和开发的那些中，最相关的新工具以及对其性能的评估。

潜在位置网络模型是网络科学的多功能工具;应用程序包括集群实体，控制因果混淆，并在未观察的图形上定义前提。估计每个节点的潜在位置通常是贝叶斯推理问题的群体，吉布斯内的大都市是最流行的近似后分布的工具。然而，众所周知，GIBBS内的大都市对于大型网络而言是低效;接受比计算成本昂贵，并且所得到的后绘高度相关。在本文中，我们提出了一个替代的马尔可夫链蒙特卡罗战略 - 使用分裂哈密顿蒙特卡罗和萤火虫蒙特卡罗的组合定义 - 利用后部分布的功能形式进行更有效的后退计算。我们展示了这些战略在吉布斯和综合网络上的其他算法中优于大都市，以及学区的教师和工作人员的真正信息共享网络。

贝叶斯变量选择是用于数据分析的强大工具，因为它为可变选择提供了原则性的方法，该方法可以说明事先信息和不确定性。但是，贝叶斯变量选择的广泛采用受到计算挑战的阻碍，尤其是在具有大量协变量P或非偶联的可能性的困难政权中。为了扩展到大型P制度，我们引入了一种有效的MCMC方案，其每次迭代的成本在P中是均等的。此外，我们还显示了如何将该方案扩展到用于计数数据的广义线性模型，这些模型在生物学，生态学，经济学，经济学，经济学，经济学，经济学，经济学，经济学上很普遍超越。特别是，我们设计有效的算法，用于二项式和负二项式回归中的可变选择，其中包括逻辑回归作为一种特殊情况。在实验中，我们证明了方法的有效性，包括对癌症和玉米基因组数据。

在过去二十年中，识别具有不同纵向数据趋势的群体的方法已经成为跨越许多研究领域的兴趣。为了支持研究人员，我们总结了文献关于纵向聚类的指导。此外，我们提供了一种纵向聚类方法，包括基于基团的轨迹建模（GBTM），生长混合模拟（GMM）和纵向K平均值（KML）。该方法在基本级别引入，并列出了强度，限制和模型扩展。在最近数据收集的发展之后，将注意这些方法的适用性赋予密集的纵向数据（ILD）。我们展示了使用R.中可用的包在合成数据集上的应用程序的应用。

我们引入了一种新的经验贝叶斯方法，用于大规模多线性回归。我们的方法结合了两个关键思想：（i）使用灵活的“自适应收缩”先验，该先验近似于正常分布的有限混合物，近似于正常分布的非参数家族； （ii）使用变分近似来有效估计先前的超参数并计算近似后期。将这两个想法结合起来，将快速，灵活的方法与计算速度相当，可与快速惩罚的回归方法（例如Lasso）相当，并在各种场景中具有出色的预测准确性。此外，我们表明，我们方法中的后验平均值可以解释为解决惩罚性回归问题，并通过直接解决优化问题（而不是通过交叉验证来调整）从数据中学到的惩罚函数的精确形式。 。我们的方法是在r https://github.com/stephenslab/mr.ash.ash.alpha的r软件包中实现的

贝叶斯变量选择是用于数据分析的强大工具，因为它为可变选择提供了原则性的方法，该方法可以说明事先信息和不确定性。但是，贝叶斯变量选择的更广泛采用受到计算挑战的阻碍，尤其是在具有大量协变量或非偶联的可能性的困难政权中。在生物学，生态学，经济学及其他方面普遍存在的计数数据的广义线性模型代表了一个重要的特殊情况。在这里，我们介绍了一种有效的MCMC方案，用于利用脾气暴躁的Gibbs采样（Zanella and Roberts，2019年）中的二项式和负二项式回归中的可变选择，其中包括逻辑回归作为一种特殊情况。在实验中，我们证明了我们的方法的有效性，包括对拥有一千万变量的癌症数据。

Many scientific problems require identifying a small set of covariates that are associated with a target response and estimating their effects. Often, these effects are nonlinear and include interactions, so linear and additive methods can lead to poor estimation and variable selection. Unfortunately, methods that simultaneously express sparsity, nonlinearity, and interactions are computationally intractable -- with runtime at least quadratic in the number of covariates, and often worse. In the present work, we solve this computational bottleneck. We show that suitable interaction models have a kernel representation, namely there exists a "kernel trick" to perform variable selection and estimation in $O$(# covariates) time. Our resulting fit corresponds to a sparse orthogonal decomposition of the regression function in a Hilbert space (i.e., a functional ANOVA decomposition), where interaction effects represent all variation that cannot be explained by lower-order effects. On a variety of synthetic and real data sets, our approach outperforms existing methods used for large, high-dimensional data sets while remaining competitive (or being orders of magnitude faster) in runtime.

离散数据丰富，并且通常作为计数或圆形数据而出现。甚至对于线性回归模型，缀合格前沿和闭合形式的后部通常是不可用的，这需要近似诸如MCMC的后部推理。对于广泛的计数和圆形数据回归模型，我们介绍了能够闭合后部推理的共轭前沿。密钥后和预测功能可通过直接蒙特卡罗模拟来计算。至关重要的是，预测分布是离散的，以匹配数据的支持，并且可以在多个协变量中进行共同评估或模拟。这些工具广泛用途是线性回归，非线性模型，通过基础扩展，以及模型和变量选择。多种仿真研究表明计算，预测性建模和相对于现有替代方案的选择性的显着优势。

Understanding of the pathophysiology of obstructive lung disease (OLD) is limited by available methods to examine the relationship between multi-omic molecular phenomena and clinical outcomes. Integrative factorization methods for multi-omic data can reveal latent patterns of variation describing important biological signal. However, most methods do not provide a framework for inference on the estimated factorization, simultaneously predict important disease phenotypes or clinical outcomes, nor accommodate multiple imputation. To address these gaps, we propose Bayesian Simultaneous Factorization (BSF). We use conjugate normal priors and show that the posterior mode of this model can be estimated by solving a structured nuclear norm-penalized objective that also achieves rank selection and motivates the choice of hyperparameters. We then extend BSF to simultaneously predict a continuous or binary response, termed Bayesian Simultaneous Factorization and Prediction (BSFP). BSF and BSFP accommodate concurrent imputation and full posterior inference for missing data, including "blockwise" missingness, and BSFP offers prediction of unobserved outcomes. We show via simulation that BSFP is competitive in recovering latent variation structure, as well as the importance of propagating uncertainty from the estimated factorization to prediction. We also study the imputation performance of BSF via simulation under missing-at-random and missing-not-at-random assumptions. Lastly, we use BSFP to predict lung function based on the bronchoalveolar lavage metabolome and proteome from a study of HIV-associated OLD. Our analysis reveals a distinct cluster of patients with OLD driven by shared metabolomic and proteomic expression patterns, as well as multi-omic patterns related to lung function decline. Software is freely available at https://github.com/sarahsamorodnitsky/BSFP .

In many applications, heterogeneous treatment effects on a censored response variable are of primary interest, and it is natural to evaluate the effects at different quantiles (e.g., median). The large number of potential effect modifiers, the unknown structure of the treatment effects, and the presence of right censoring pose significant challenges. In this paper, we develop a hybrid forest approach called Hybrid Censored Quantile Regression Forest (HCQRF) to assess the heterogeneous effects varying with high-dimensional variables. The hybrid estimation approach takes advantage of the random forests and the censored quantile regression. We propose a doubly-weighted estimation procedure that consists of a redistribution-of-mass weight to handle censoring and an adaptive nearest neighbor weight derived from the forest to handle high-dimensional effect functions. We propose a variable importance decomposition to measure the impact of a variable on the treatment effect function. Extensive simulation studies demonstrate the efficacy and stability of HCQRF. The result of the simulation study also convinces us of the effectiveness of the variable importance decomposition. We apply HCQRF to a clinical trial of colorectal cancer. We achieve insightful estimations of the treatment effect and meaningful variable importance results. The result of the variable importance also confirms the necessity of the decomposition.

在选择组套索（或普遍的变体，例如重叠，稀疏或标准化的组套索）之后，在没有选择偏见的调整的情况下，对所选参数的推断是不可靠的。在受惩罚的高斯回归设置中，现有方法为选择事件提供了调整，这些事件可以表示为数据变量中的线性不平等。然而，这种表示未能与组套索一起选择，并实质上阻碍了随后的选择后推断的范围。推论兴趣的关键问题 - 例如，推断选定变量对结果的影响 - 仍未得到解答。在本文中，我们开发了一种一致的，选择性的贝叶斯方法，通过得出似然调整因子和近似值来解决现有差距，从而消除了组中的偏见。对模拟数据和人类Connectome项目数据的实验表明，我们的方法恢复了所选组中参数的影响，同时仅支付较小的偏差调整价格。

在许多科学应用中出现了从一组共同样本中获得两种（或更多）类型的测量的数据集。此类数据的探索性分析中的一个常见问题是识别有密切相关的不同数据类型的特征组。 Bimodule是来自两种数据类型的特征集的一对（A，B），因此A和B中的特征之间的汇总相关很大。如果A与B中的特征显着相关的特征集合，则BIMODULE（A，B）是稳定的，反之亦然。在本文中，我们提出并研究了基于迭代测试的程序（BSP），以识别Bi-View数据中稳定的双模型。我们进行了一项彻底的模拟研究，以评估BSP的性能，并使用GTEX项目的最新数据提出了表达定量性状基因座（EQTL）分析问题的扩展应用。此外，我们将BSP应用于气候数据，以确定北美地区年温度变化影响降水的区域。

重要的加权是调整蒙特卡洛集成以说明错误分布中抽取的一种一般方法，但是当重要性比的右尾巴较重时，最终的估计值可能是高度可变的。当目标分布的某些方面无法通过近似分布捕获，在这种情况下，可以通过修改极端重要性比率来获得更稳定的估计。我们提出了一种新的方法，该方法使用拟合模拟重要性比率的上尾的广义帕累托分布来稳定重要性权重。该方法在经验上的性能要比现有方法稳定重要性采样估计值更好，包括稳定的有效样本量估计，蒙特卡洛误差估计和收敛诊断。提出的帕累托$ \ hat {k} $有限样本收敛率诊断对任何蒙特卡洛估计器都有用。

Prognostication for lung cancer, a leading cause of mortality, remains a complex task, as it needs to quantify the associations of risk factors and health events spanning a patient's entire life. One challenge is that an individual's disease course involves non-terminal (e.g., disease progression) and terminal (e.g., death) events, which form semi-competing relationships. Our motivation comes from the Boston Lung Cancer Study, a large lung cancer survival cohort, which investigates how risk factors influence a patient's disease trajectory. Following developments in the prediction of time-to-event outcomes with neural networks, deep learning has become a focal area for the development of risk prediction methods in survival analysis. However, limited work has been done to predict multi-state or semi-competing risk outcomes, where a patient may experience adverse events such as disease progression prior to death. We propose a novel neural expectation-maximization algorithm to bridge the gap between classical statistical approaches and machine learning. Our algorithm enables estimation of the non-parametric baseline hazards of each state transition, risk functions of predictors, and the degree of dependence among different transitions, via a multi-task deep neural network with transition-specific sub-architectures. We apply our method to the Boston Lung Cancer Study and investigate the impact of clinical and genetic predictors on disease progression and mortality.

We develop a Bayesian semi-parametric model for the estimating the impact of dynamic treatment rules on survival among patients diagnosed with pediatric acute myeloid leukemia (AML). The data consist of a subset of patients enrolled in the phase III AAML1031 clinical trial in which patients move through a sequence of four treatment courses. At each course, they undergo treatment that may or may not include anthracyclines (ACT). While ACT is known to be effective at treating AML, it is also cardiotoxic and can lead to early death for some patients. Our task is to estimate the potential survival probability under hypothetical dynamic ACT treatment strategies, but there are several impediments. First, since ACT was not randomized in the trial, its effect on survival is confounded over time. Second, subjects initiate the next course depending on when they recover from the previous course, making timing potentially informative of subsequent treatment and survival. Third, patients may die or drop out before ever completing the full treatment sequence. We develop a generative Bayesian semi-parametric model based on Gamma Process priors to address these complexities. At each treatment course, the model captures subjects' transition to subsequent treatment or death in continuous time under a given rule. A g-computation procedure is used to compute a posterior over potential survival probability that is adjusted for time-varying confounding. Using this approach, we conduct posterior inference for the efficacy of hypothetical treatment rules that dynamically modify ACT based on evolving cardiac function.