Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We profiled 45,000 immune cells from ...eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer. Our results have important implications for characterizing tumor-infiltrating immune cells.
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•Single-cell RNA-seq reveals phenotypic expansion of intratumoral immune cells•Biscuit identifies cell populations that differ in co-expression patterns•T cells reside on continuous activation and differentiation trajectories•Combinatorial environmental inputs and TCR usage shape T cell phenotypes
Single-cell analysis of the breast tumor immune microenvironment, coupled with computational analysis, yields an immune map of breast cancer that points to continuous T cell activation and differentiation states.
Recent single-cell analysis technologies offer an unprecedented opportunity to elucidate developmental pathways. Here we present Wishbone, an algorithm for positioning single cells along bifurcating ...developmental trajectories with high resolution. Wishbone uses multi-dimensional single-cell data, such as mass cytometry or RNA-Seq data, as input and orders cells according to their developmental progression, and it pinpoints bifurcation points by labeling each cell as pre-bifurcation or as one of two post-bifurcation cell fates. Using 30-channel mass cytometry data, we show that Wishbone accurately recovers the known stages of T-cell development in the mouse thymus, including the bifurcation point. We also apply the algorithm to mouse myeloid differentiation and demonstrate its generalization to additional lineages. A comparison of Wishbone to diffusion maps, SCUBA and Monocle shows that it outperforms these methods both in the accuracy of ordering cells and in the correct identification of branch points.
Social media messages posted by people during natural disasters often contain important location descriptions, such as the locations of victims. Recent research has shown that many of these location ...descriptions go beyond simple place names, such as city names and street names, and are difficult to extract using typical named entity recognition (NER) tools. While advanced machine learning models could be trained, they require large labeled training datasets that can be time-consuming and labor-intensive to create. In this work, we propose a method that fuses geo-knowledge of location descriptions and a Generative Pre-trained Transformer (GPT) model, such as ChatGPT and GPT-4. The result is a geo-knowledge-guided GPT model that can accurately extract location descriptions from disaster-related social media messages. Also, only 22 training examples encoding geo-knowledge are used in our method. We conduct experiments to compare this method with nine alternative approaches on a dataset of tweets from Hurricane Harvey. Our method demonstrates an over 40% improvement over typically used NER approaches. The experiment results also show that geo-knowledge is indispensable for guiding the behavior of GPT models. The extracted location descriptions can help disaster responders reach victims more quickly and may even save lives.
Compression and efficient storage of neural network (NN) parameters is critical for applications that run on resource-constrained devices. Despite the significant progress in NN model compression, ...there has been considerably less investigation in the actual physical storage of NN parameters. Conventionally, model compression and physical storage are decoupled, as digital storage media with error-correcting codes (ECCs) provide robust error-free storage. However, this decoupled approach is inefficient as it ignores the overparameterization present in most NNs and forces the memory device to allocate the same amount of resources to every bit of information regardless of its importance. In this work, we investigate analog memory devices as an alternative to digital media – one that naturally provides a way to add more protection for significant bits unlike its counterpart, but is noisy and may compromise the stored model’s performance if used naively. We develop a variety of robust coding strategies for NN weight storage on analog devices, and propose an approach to jointly optimize model compression and memory resource allocation. We then demonstrate the efficacy of our approach on models trained on MNIST, CIFAR-10, and ImageNet datasets for existing compression techniques. Compared to conventional error-free digital storage, our method reduces the memory footprint by up to one order of magnitude, without significantly compromising the stored model’s accuracy.
Large pre-trained models, also known as foundation models (FMs), are trained in a task-agnostic manner on large-scale data and can be adapted to a wide range of downstream tasks by fine tuning, ...few-shot, or even zero-shot learning. Despite their successes in language and vision tasks, we have yet to see an attempt to develop foundation models for geospatial artificial intelligence (GeoAI). In this work, we explore the promises and challenges for developing multimodal foundation models for GeoAI. We first show the advantages of this idea by testing the performance of existing Large pre-trained Language Models (LLMs) (e.g. GPT-2 and GPT-3) on two geospatial semantics tasks. Results indicate that these task-agnostic LLMs can outperform task-specific fully-supervised models on both tasks with 2--9% improvement in a few-shot learning setting. However, we also show the limitations of these existing foundation models given the multimodality nature of GeoAI, especially when dealing with geometries in conjunction with other modalities. So we discuss the possibility of a multimodal foundation model which can reason over various types of geospatial data through geospatial alignments. We conclude this paper by discussing the unique risks and challenges to develop such model for GeoAI.
Density ratio estimation serves as an important technique in the unsupervised machine learning toolbox. However, such ratios are difficult to estimate for complex, high-dimensional data, particularly ...when the densities of interest are sufficiently different. In our work, we propose to leverage an invertible generative model to map the two distributions into a common feature space prior to estimation. This featurization brings the densities closer together in latent space, sidestepping pathological scenarios where the learned density ratios in input space can be arbitrarily inaccurate. At the same time, the invertibility of our feature map guarantees that the ratios computed in feature space are equivalent to those in input space. Empirically, we demonstrate the efficacy of our approach in a variety of downstream tasks that require access to accurate density ratios such as mutual information estimation, targeted sampling in deep generative models, and classification with data augmentation.
Representing probability distributions by the gradient of their density functions has proven effective in modeling a wide range of continuous data modalities. However, this representation is not ...applicable in discrete domains where the gradient is undefined. To this end, we propose an analogous score function called the "Concrete score", a generalization of the (Stein) score for discrete settings. Given a predefined neighborhood structure, the Concrete score of any input is defined by the rate of change of the probabilities with respect to local directional changes of the input. This formulation allows us to recover the (Stein) score in continuous domains when measuring such changes by the Euclidean distance, while using the Manhattan distance leads to our novel score function in discrete domains. Finally, we introduce a new framework to learn such scores from samples called Concrete Score Matching (CSM), and propose an efficient training objective to scale our approach to high dimensions. Empirically, we demonstrate the efficacy of CSM on density estimation tasks on a mixture of synthetic, tabular, and high-dimensional image datasets, and demonstrate that it performs favorably relative to existing baselines for modeling discrete data.
Normalizing flows model complex probability distributions using maps obtained by composing invertible layers. Special linear layers such as masked and 1x1 convolutions play a key role in existing ...architectures because they increase expressive power while having tractable Jacobians and inverses. We propose a new family of invertible linear layers based on butterfly layers, which are known to theoretically capture complex linear structures including permutations and periodicity, yet can be inverted efficiently. This representational power is a key advantage of our approach, as such structures are common in many real-world datasets. Based on our invertible butterfly layers, we construct a new class of normalizing flow models called ButterflyFlow. Empirically, we demonstrate that ButterflyFlows not only achieve strong density estimation results on natural images such as MNIST, CIFAR-10, and ImageNet 32x32, but also obtain significantly better log-likelihoods on structured datasets such as galaxy images and MIMIC-III patient cohorts -- all while being more efficient in terms of memory and computation than relevant baselines.
Density ratio estimation (DRE) is a fundamental machine learning technique for comparing two probability distributions. However, existing methods struggle in high-dimensional settings, as it is ...difficult to accurately compare probability distributions based on finite samples. In this work we propose DRE-\infty, a divide-and-conquer approach to reduce DRE to a series of easier subproblems. Inspired by Monte Carlo methods, we smoothly interpolate between the two distributions via an infinite continuum of intermediate bridge distributions. We then estimate the instantaneous rate of change of the bridge distributions indexed by time (the "time score") -- a quantity defined analogously to data (Stein) scores -- with a novel time score matching objective. Crucially, the learned time scores can then be integrated to compute the desired density ratio. In addition, we show that traditional (Stein) scores can be used to obtain integration paths that connect regions of high density in both distributions, improving performance in practice. Empirically, we demonstrate that our approach performs well on downstream tasks such as mutual information estimation and energy-based modeling on complex, high-dimensional datasets.
Meta-Amortized Variational Inference and Learning Wu, Mike; Choi, Kristy; Goodman, Noah ...
Proceedings of the ... AAAI Conference on Artificial Intelligence,
04/2020, Letnik:
34, Številka:
4
Journal Article
Despite the recent success in probabilistic modeling and their applications, generative models trained using traditional inference techniques struggle to adapt to new distributions, even when the ...target distribution may be closely related to the ones seen during training. In this work, we present a doubly-amortized variational inference procedure as a way to address this challenge. By sharing computation across not only a set of query inputs, but also a set of different, related probabilistic models, we learn transferable latent representations that generalize across several related distributions. In particular, given a set of distributions over images, we find the learned representations to transfer to different data transformations. We empirically demonstrate the effectiveness of our method by introducing the MetaVAE, and show that it significantly outperforms baselines on downstream image classification tasks on MNIST (10-50%) and NORB (10-35%).
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