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We develop a general framework for distribution-free predictive inference in regression, using conformal inference. The proposed methodology allows for the construction of a prediction band for the response variable using any estimator of the regression function. The resulting prediction band preserves the consistency properties of the original estimator under standard assumptions, while guaranteeing finite-sample marginal coverage even when these assumptions do not hold. We analyze and compare, both empirically and theoretically, the two major variants of our conformal framework: full conformal inference and split conformal inference, along with a related jackknife method. These methods offer different tradeoffs between statistical accuracy (length of resulting prediction intervals) and computational efficiency. As extensions, we develop a method for constructing valid in-sample prediction intervals called rank-one-out conformal inference, which has essentially the same computational efficiency as split conformal inference. We also describe an extension of our procedures for producing prediction bands with locally varying length, to adapt to heteroscedasticity in the data. Finally, we propose a model-free notion of variable importance, called leave-one-covariate-out or LOCO inference. Accompanying this article is an R package conformalInference that implements all of the proposals we have introduced. In the spirit of reproducibility, all of our empirical results can also be easily (re)generated using this package.

Several new methods have been recently proposed for performing valid inference after model selection. An older method is sample splitting: use part of the data for model selection and the rest for inference. In this paper, we revisit sample splitting combined with the bootstrap (or the Normal approximation). We show that this leads to a simple, assumption-lean approach to inference and we establish results on the accuracy of the method. In fact, we find new bounds on the accuracy of the bootstrap and the Normal approximation for general nonlinear parameters with increasing dimension which we then use to assess the accuracy of regression inference. We define new parameters that measure variable importance and that can be inferred with greater accuracy than the usual regression coefficients. Finally, we elucidate an inference-prediction trade-off: splitting increases the accuracy and robustness of inference but can decrease the accuracy of the predictions.

Recently, Tibshirani et al. [J. Amer. Statist. Assoc. 111 (2016) 600–620] proposed a method for making inferences about parameters defined by model selection, in a typical regression setting with normally distributed errors. Here, we study the large sample properties of this method, without assuming normality. We prove that the test statistic of Tibshirani et al. (2016) is asymptotically valid, as the number of samples n grows and the dimension d of the regression problem stays fixed. Our asymptotic result holds uniformly over a wide class of nonnormal error distributions. We also propose an efficient bootstrap version of this test that is provably (asymptotically) conservative, and in practice, often delivers shorter intervals than those from the original normality-based approach. Finally, we prove that the test statistic of Tibshirani et al. (2016) does not enjoy uniform validity in a high-dimensional setting, when the dimension d is allowed grow.

We consider estimating an unknown signal, both blocky and sparse, which is corrupted by additive noise. We study three interrelated least squares procedures and their asymptotic properties. The first procedure is the fused lasso, put forward by Friedman et al. [Ann. Appl. Statist. 1 (2007) 302-332], which we modify into a different estimator, called the fused adaptive lasso, with better properties. The other two estimators we discuss solve least squares problems on sieves; one constrains the maximal ℓ₁ norm and the maximal total variation seminorm, and the other restricts the number of blocks and the number of nonzero coordinates of the signal. We derive conditions for the recovery of the true block partition and the true sparsity patterns by the fused lasso and the fused adaptive lasso, and we derive convergence rates for the sieve estimators, explicitly in terms of the constraining parameters.

We analyze the performance of spectral clustering for community extraction in stochastic block models. We show that, under mild conditions, spectral clustering applied to the adjacency matrix of the network can consistently recover hidden communities even when the order of the maximum expected degree is as small as log n, with n the number of nodes. This result applies to some popular polynomial time spectral clustering algorithms and is further extended to degree corrected stochastic block models using a spherical k-median spectral clustering method. A key component of our analysis is a combinatorial bound on the spectrum of binary random matrices, which is sharper than the conventional matrix Bernstein inequality and may be of independent interest.

We study the problem of change point localization in dynamic networks models.We assume that we observe a sequence of independent adjacency matrices of the same size, each corresponding to a realization of an unknown inhomogeneous Bernoulli model. The underlying distribution of the adjacency matrices are piecewise constant, and may change over a subset of the time points, called change points. We are concerned with recovering the unknown number and positions of the change points. In our model setting, we allow for all the model parameters to change with the total number of time points, including the network size, the minimal spacing between consecutive change points, the magnitude of the smallest change and the degree of sparsity of the networks. We first identify a region of impossibility in the space of the model parameters such that no change point estimator is provably consistent if the data are generated according to parameters falling in that region. We propose a computationally-simple algorithm for network change point localization, called network binary segmentation, that relies on weighted averages of the adjacency matrices.We show that network binary segmentation is consistent over a range of the model parameters that nearly cover the complement of the impossibility region, thus demonstrating the existence of a phase transition for the problem at hand. Next, we devise a more sophisticated algorithm based on singular value thresholding, called local refinement, that delivers more accurate estimates of the change point locations. Under appropriate conditions, local refinement guarantees a minimax optimal rate for network change point localization while remaining computationally feasible.

We study generalized density-based clustering in which sharply defined clusters such as clusters on lower-dimensional manifolds are allowed. We show that accurate clustering is possible even in high dimensions. We propose two data-based methods for choosing the bandwidth and we study the stability properties of density clusters. We show that a simple graph-based algorithm successfully approximates the high density clusters.

The growing availability of network data and of scientific interest in distributed systems has led to the rapid development of statistical models of net-work structure. Typically, however, these are models for the entire network, while the data consists only of a sampled sub-network. Parameters for the whole network, which is what is of interest, are estimated by applying the model to the sub-network. This assumes that the model is consistent under sampling, or, in terms of the theory of stochastic processes, that it defines a projective family. Focusing on the popular class of exponential random graph models (ERGMs), we show that this apparently trivial condition is in fact violated by many popular and scientifically appealing models, and that satisfying it drastically limits ERGM's expressive power. These results are actually special cases of more general results about exponential families of dependent random variables, which we also prove. Using such results, we offer easily checked conditions for the consistency of maximum likelihood estimation in ERGMs, and discuss some possible constructive responses.

Background Thymoma is an uncommon cancer often associated with myasthenia gravis, an autoimmune disorder of the neuromuscular junction characterized by muscular fatigability. In patients with advanced nonmetastatic thymoma, primary chemotherapy may be required to induce tumor shrinkage and to achieve radical resection. Cancer chemotherapy has been anecdotally reported as a trigger factor for worsening of myasthenia gravis in thymic epithelial cancers. The study of uncommon cases of chemotherapy-related myasthenic crisis is warranted to gain knowledge of clinical situations requiring intensive care support in the case of life-threatening respiratory failure. Case presentation We report a case of an 18-year-old Caucasian woman with advanced Masaoka-Koga stage III type B2 thymoma and myasthenia gravis on treatment with pyridostigmine, steroids and intravenous immunoglobulins, who developed a myasthenic crisis 2 hours after initiation of cyclophosphamide/doxorubicin/cisplatin primary chemotherapy. Because of severe acute respiratory failure, emergency tracheal intubation, mechanical ventilation, and temporary (2 hours) discontinuation of chemotherapy were needed. Considering the curative intent of the multimodal therapeutic program, we elected to resume primary chemotherapy administration while the patient remained on mechanical ventilation. After 24 hours, the recovery of adequate respiratory function allowed successful weaning from respiratory support, and no further adverse events occurred. After 3 weeks, upon plasma exchange initiation with amelioration of myasthenic symptoms, a second course of chemotherapy was given, and in week 6, having documented partial tumor remission, the patient underwent radical surgery (R0) and then consolidation radiation therapy with 50.4 Gy in 28 fractions in weeks 15–20. Conclusions This case report, together with the only four available in a review of the literature, highlights that chemotherapy may carry the risk of myasthenic crisis in patients affected by thymoma and myasthenia gravis. To our knowledge, this is the first reported case of chemotherapy continuation on mechanical ventilation in a patient with chemotherapy-induced myasthenic crisis requiring tracheal intubation. The lesson learned from the present case is that, in selected cases of advanced thymoma, the paradoxical worsening of myasthenia gravis during chemotherapy should not be considered an absolute contraindication for the continuation of primary chemotherapy with curative intent.