Causal inference involving Structural causal models (SCMs) provides a principled approach to identifying causation from observational and experimental data in disciplines ranging from economics to medicine. However, to estimate the underlying causal structure, SCMs need to rely on domain knowledge in addition to available data. Clinical research has a vast collection of well-explored hypotheses, experiments, and publications, rich with underused causal information. A key challenge in this context is the absence (or acceptance) of a systematic and methodological framework for encoding priors (background knowledge) into causal models. We propose an abstraction called causal knowledge hierarchy (CKH) for encoding priors into causal models. Our approach is based on the foundation of "levels of evidence" in medicine, with a focus on confidence in causal information. Using CKH, we present a standardized framework for encoding causal priors from various information sources and combining them to derive an SCM. We evaluate our approach on multiple (simulated and real-world) benchmark datasets and demonstrate overall performance compared to the ground truth causal model.

First-order optimization techniques, such as stochastic gradient descent (SGD) and its variants, are widely used in machine learning applications due to their simplicity and low per-iteration costs. However, they often require larger numbers of iterations, with associated communication costs in distributed environments. In contrast, Newton-type methods, while having higher per-iteration computation costs, typically require a significantly smaller number of iterations, which directly translates to reduced communication costs. We present a novel distributed optimizer for classification problems, which integrates a GPU-accelerated Newton-type solver with the global consensus formulation of Alternating Direction of Method Multipliers (ADMM). By leveraging the communication efficiency of ADMM, a highly efficient GPUaccelerated inexact-Newton solver, and an effective spectral penalty parameter selection strategy, we show that our proposed method (i) yields better generalization performance on several classification problems; (ii) significantly outperforms state-of-the-art methods in distributed time to solution; and (iii) offers better scaling on large distributed platforms.

BACKGROUND: The data deluge can leverage sophisticated ML techniques for functionally annotating the regulatory non-coding genome. The challenge lies in selecting the appropriate classifier for the specific functional annotation problem, within the bounds of the hardware constraints and the model's complexity. In our system AIKYATAN, we annotate distal epigenomic regulatory sites, e.g., enhancers. Specifically, we develop a binary classifier that classifies genome sequences as distal regulatory regions or not, given their histone modifications' combinatorial signatures. This problem is challenging because the regulatory regions are distal to the genes, with diverse signatures across classes (e.g., enhancers and insulators) and even within each class (e.g., different enhancer sub-classes). RESULTS: We develop a suite of ML models, under the banner AIKYATAN, including SVM models, random forest variants, and deep learning architectures, for distal regulatory element (DRE) detection. We demonstrate, with strong empirical evidence, deep learning approaches have a computational advantage. Plus, convolutional neural networks (CNN) provide the best-in-class accuracy, superior to the vanilla variant. With the human embryonic cell line H1, CNN achieves an accuracy of 97.9% and an order of magnitude lower runtime than the kernel SVM. Running on a GPU, the training time is sped up 21x and 30x (over CPU) for DNN and CNN, respectively. Finally, our CNN model enjoys superior prediction performance vis-'a-vis the competition. Specifically, AIKYATAN-CNN achieved 40% higher validation rate versus CSIANN and the same accuracy as RFECS. CONCLUSIONS: Our exhaustive experiments using an array of ML tools validate the need for a model that is not only expressive but can scale with increasing data volumes and diversity. In addition, a subset of these datasets have image-like properties and benefit from spatial pooling of features. Our AIKYATAN suite leverages diverse epigenomic datasets that can then be modeled using CNNs with optimized activation and pooling functions. The goal is to capture the salient features of the integrated epigenomic datasets for deciphering the distal (non-coding) regulatory elements, which have been found to be associated with functional variants. Our source code will be made publicly available at: https://bitbucket.org/cellsandmachines/aikyatan.