CRISPR genome engineering and single-cell RNA sequencing have transformed biological discovery. Single-cell CRISPR screens unite these two technologies, linking genetic perturbations in individual cells to changes in gene expression and illuminating regulatory networks underlying diseases. Despite their promise, single-cell CRISPR screens present substantial statistical challenges. We demonstrate through theoretical and real data analyses that a standard method for estimation and inference in single-cell CRISPR screens -- "thresholded regression" -- exhibits attenuation bias and a bias-variance tradeoff as a function of an intrinsic, challenging-to-select tuning parameter. To overcome these difficulties, we introduce GLM-EIV ("GLM-based errors-in-variables"), a new method for single-cell CRISPR screen analysis. GLM-EIV extends the classical errors-in-variables model to responses and noisy predictors that are exponential family-distributed and potentially impacted by the same set of confounding variables. We develop a computational infrastructure to deploy GLM-EIV across tens or hundreds of nodes on clouds (e.g., Microsoft Azure) and high-performance clusters. Leveraging this infrastructure, we apply GLM-EIV to analyze two recent, large-scale, single-cell CRISPR screen datasets, demonstrating improved performance in challenging problem settings.
Common tasks encountered in epidemiology, including disease incidence estimation and causal inference, rely on predictive modeling. Constructing a predictive model can be thought of as learning a prediction function, i.e., a function that takes as input covariate data and outputs a predicted value. Many strategies for learning these functions from data are available, from parametric regressions to machine learning algorithms. It can be challenging to choose an approach, as it is impossible to know in advance which one is the most suitable for a particular dataset and prediction task at hand. The super learner (SL) is an algorithm that alleviates concerns over selecting the one "right" strategy while providing the freedom to consider many of them, such as those recommended by collaborators, used in related research, or specified by subject-matter experts. It is an entirely pre-specified and data-adaptive strategy for predictive modeling. To ensure the SL is well-specified for learning the prediction function, the analyst does need to make a few important choices. In this Education Corner article, we provide step-by-step guidelines for making these choices, walking the reader through each of them and providing intuition along the way. In doing so, we aim to empower the analyst to tailor the SL specification to their prediction task, thereby ensuring their SL performs as well as possible. A flowchart provides a concise, easy-to-follow summary of key suggestions and heuristics, based on our accumulated experience, and guided by theory.
For relational structures A, B of the same signature, the Promise Constraint Satisfaction Problem PCSP(A,B) asks whether a given input structure maps homomorphically to A or does not even map to B. We are promised that the input satisfies exactly one of these two cases. If there exists a structure C with homomorphisms $A\to C\to B$, then PCSP(A,B) reduces naturally to CSP(C). To the best of our knowledge all known tractable PCSPs reduce to tractable CSPs in this way. However Barto showed that some PCSPs over finite structures A, B require solving CSPs over infinite C. We show that even when such a reduction to finite C is possible, this structure may become arbitrarily large. For every integer $n>1$ and every prime p we give A, B of size n with a single relation of arity $n^p$ such that PCSP(A, B) reduces via a chain of homomorphisms $ A\to C\to B$ to a tractable CSP over some C of size p but not over any smaller structure. In a second family of examples, for every prime $p\geq 7$ we construct A, B of size $p-1$ with a single ternary relation such that PCSP(A, B) reduces via $A\to C\to B$ to a tractable CSP over some C of size p but not over any smaller structure. In contrast we show that if A, B are graphs and PCSP(A,B) reduces to tractable CSP(C) for some finite digraph C, then already A or B has a tractable CSP. This extends results and answers a question of Deng et al.
In a sports competition, a team might lose a powerful incentive to exert full effort if its final rank does not depend on the outcome of the matches still to be played. Therefore, the organiser should reduce the probability of such a situation to the extent possible. Our paper provides a classification scheme to identify these weakly (where one team is indifferent) or strongly (where both teams are indifferent) stakeless games. A statistical model is estimated to simulate the UEFA Champions League groups and compare the candidate schedules used in the 2021/22 season according to the competitiveness of the matches played in the last round(s). The option followed in four of the eight groups is found to be optimal under a wide set of parameters. Minimising the number of strongly stakeless matches is verified to be a likely goal in the computer draw of the fixture that remains hidden from the public.
Linear mixed models (LMMs) are instrumental for regression analysis with structured dependence, such as grouped, clustered, or multilevel data. However, selection among the covariates--while accounting for this structured dependence--remains a challenge. We introduce a Bayesian decision analysis for subset selection with LMMs. Using a Mahalanobis loss function that incorporates the structured dependence, we derive optimal linear coefficients for (i) any given subset of variables and (ii) all subsets of variables that satisfy a cardinality constraint. Crucially, these estimates inherit shrinkage or regularization and uncertainty quantification from the underlying Bayesian model, and apply for any well-specified Bayesian LMM. More broadly, our decision analysis strategy deemphasizes the role of a single "best" subset, which is often unstable and limited in its information content, and instead favors a collection of near-optimal subsets. This collection is summarized by key member subsets and variable-specific importance metrics. Customized subset search and out-of-sample approximation algorithms are provided for more scalable computing. These tools are applied to simulated data and a longitudinal physical activity dataset, and demonstrate excellent prediction, estimation, and selection ability.
Pretrained language models can be effectively stimulated by textual prompts or demonstrations, especially in low-data scenarios. Recent works have focused on automatically searching discrete or continuous prompts or optimized verbalizers, yet studies for the demonstration are still limited. Concretely, the demonstration examples are crucial for an excellent final performance of prompt-tuning. In this paper, we propose a novel pluggable, extensible, and efficient approach named contrastive demonstration tuning, which is free of demonstration sampling. Furthermore, the proposed approach can be: (i) Plugged to any previous prompt-tuning approaches; (ii) Extended to widespread classification tasks with a large number of categories. Experimental results on 16 datasets illustrate that our method integrated with previous approaches LM-BFF and P-tuning can yield better performance. Code is available in //github.com/zjunlp/PromptKG/tree/main/research/Demo-Tuning.
We consider M-estimation problems, where the target value is determined using a minimizer of an expected functional of a Levy process. With discrete observations from the Levy process, we can produce a "quasi-path" by shuffling increments of the Levy process, we call it a quasi-process. Under a suitable sampling scheme, a quasi-process can converge weakly to the true process according to the properties of the stationary and independent increments. Using this resampling technique, we can estimate objective functionals similar to those estimated using the Monte Carlo simulations, and it is available as a contrast function. The M-estimator based on these quasi-processes can be consistent and asymptotically normal.
In the interdependent values (IDV) model introduced by Milgrom and Weber [1982], agents have private signals that capture their information about different social alternatives, and the valuation of every agent is a function of all agent signals. While interdependence has been mainly studied for auctions, it is extremely relevant for a large variety of social choice settings, including the canonical setting of public projects. The IDV model is very challenging relative to standard independent private values, and welfare guarantees have been achieved through two alternative conditions known as {\em single-crossing} and {\em submodularity over signals (SOS)}. In either case, the existing theory falls short of solving the public projects setting. Our contribution is twofold: (i) We give a workable characterization of truthfulness for IDV public projects for the largest class of valuations for which such a characterization exists, and term this class \emph{decomposable valuations}; (ii) We provide possibility and impossibility results for welfare approximation in public projects with SOS valuations. Our main impossibility result is that, in contrast to auctions, no universally truthful mechanism performs better for public projects with SOS valuations than choosing a project at random. Our main positive result applies to {\em excludable} public projects with SOS, for which we establish a constant factor approximation similar to auctions. Our results suggest that exclusion may be a key tool for achieving welfare guarantees in the IDV model.
Bayesian phylogenetic inference is currently done via Markov chain Monte Carlo (MCMC) with simple proposal mechanisms. This hinders exploration efficiency and often requires long runs to deliver accurate posterior estimates. In this paper, we present an alternative approach: a variational framework for Bayesian phylogenetic analysis. We propose combining subsplit Bayesian networks, an expressive graphical model for tree topology distributions, and a structured amortization of the branch lengths over tree topologies for a suitable variational family of distributions. We train the variational approximation via stochastic gradient ascent and adopt gradient estimators for continuous and discrete variational parameters separately to deal with the composite latent space of phylogenetic models. We show that our variational approach provides competitive performance to MCMC, while requiring much less computation due to a more efficient exploration mechanism enabled by variational inference. Experiments on a benchmark of challenging real data Bayesian phylogenetic inference problems demonstrate the effectiveness and efficiency of our methods.
It is shown, with two sets of indicators that separately load on two distinct factors, independent of one another conditional on the past, that if it is the case that at least one of the factors causally affects the other, then, in many settings, the process will converge to a factor model in which a single factor will suffice to capture the covariance structure among the indicators. Factor analysis with one wave of data can then not distinguish between factor models with a single factor versus those with two factors that are causally related. Therefore, unless causal relations between factors can be ruled out a priori, alleged empirical evidence from one-wave factor analysis for a single factor still leaves open the possibilities of a single factor or of two factors that causally affect one another. The implications for interpreting the factor structure of psychological scales, such as self-report scales for anxiety and depression, or for happiness and purpose, are discussed. The results are further illustrated through simulations to gain insight into the practical implications of the results in more realistic settings prior to the convergence of the processes. Some further generalizations to an arbitrary number of underlying factors are noted.
With the rapid increase of large-scale, real-world datasets, it becomes critical to address the problem of long-tailed data distribution (i.e., a few classes account for most of the data, while most classes are under-represented). Existing solutions typically adopt class re-balancing strategies such as re-sampling and re-weighting based on the number of observations for each class. In this work, we argue that as the number of samples increases, the additional benefit of a newly added data point will diminish. We introduce a novel theoretical framework to measure data overlap by associating with each sample a small neighboring region rather than a single point. The effective number of samples is defined as the volume of samples and can be calculated by a simple formula $(1-\beta^{n})/(1-\beta)$, where $n$ is the number of samples and $\beta \in [0,1)$ is a hyperparameter. We design a re-weighting scheme that uses the effective number of samples for each class to re-balance the loss, thereby yielding a class-balanced loss. Comprehensive experiments are conducted on artificially induced long-tailed CIFAR datasets and large-scale datasets including ImageNet and iNaturalist. Our results show that when trained with the proposed class-balanced loss, the network is able to achieve significant performance gains on long-tailed datasets.