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Single cell profiling techniques including multi-omics and spatial-omics technologies allow researchers to study cell-cell variation within a cell population. These variations extend to biological networks within cells, in particular, the gene regulatory networks (GRNs). GRNs rewire as the cells evolve, and different cells can have different governing GRNs. However, existing GRN inference methods usually infer a single GRN for a population of cells, without exploring the cell-cell variation in terms of their regulatory mechanisms. Recently, jointly profiled single cell transcriptomics and chromatin accessibility data have been used to infer GRNs. Although methods based on such multi-omics data were shown to improve over the accuracy of methods using only single cell RNA-seq (scRNA-seq) data, they do not take full advantage of the single cell resolution chromatin accessibility data.

We propose CeSpGRN (CellSpecificGeneRegulatoryNetwork inference), which infers cell-specific GRNs from scRNA-seq, single cell multi-omics, or single cell spatial-omics data. CeSpGRN uses a Gaussian weighted kernel that allows the GRN of a given cell to be learned from the sequencing profile of itself and its neighboring cells in the developmental process. The kernel is constructed from the similarity of gene expressions or spatial locations between cells. When the chromatin accessibility data is available, CeSpGRN constructs cell-specific prior networks which are used to further improve the inference accuracy.

We applied CeSpGRN to various types of real-world datasets and inferred various regulation changes that were shown to be important in cell development. We also quantitatively measured the performance of CeSpGRN on simulated datasets and compared with baseline methods. The results show that CeSpGRN has a superior performance in reconstructing the GRN for each cell, as well as in detecting the regulatory interactions that differ between cells. CeSpGRN is available athttps://github.com/PeterZZQ/CeSpGRN.

 

Deep learning and symbolic reasoning are complementary techniques for an intelligent system. However, principled combinations of these techniques are typically limited in scalability, rendering them ill-suited for real-world applications. We propose Scallop, a system that builds upon probabilistic deductive databases, to bridge this gap. The key insight underlying Scallop is a provenance framework that introduces a tunable parameter to specify the level of reasoning granularity. Scallop thereby i) generalizes exact probabilistic reasoning, ii) asymptotically reduces computational cost, and iii) provides relative accuracy guarantees. On synthetic tasks involving mathematical and logical reasoning, Scallop scales significantly better without sacrificing accuracy compared to DeepProbLog, a principled neural logic programming approach. Scallop also scales to a newly created real-world Visual Question Answering (VQA) benchmark that requires multi-hop reasoning, achieving 84.22% accuracy and outperforming two VQA-tailored models based on Neural Module Networks and transformers by 12.42% and 21.66% respectively. 

Software APIs exhibit rich diversity and complexity which not only renders them a common source of programming errors but also hinders program analysis tools for checking them. Such tools either expect a precise API specification, which requires program analysis expertise, or presume that correct API usages follow simple idioms that can be automatically mined from code, which suffers from poor accuracy. We propose a new approach that allows regular programmers to find API misuses. Our approach interacts with the user to classify valid and invalid usages of each target API method. It minimizes user burden by employing an active learning algorithm that ranks API usages by their likelihood of being invalid. We implemented our approach in a tool called ARBITRAR for C/C++ programs, and applied it to check the uses of 18 API methods in 21 large real-world programs, including OpenSSL and Linux Kernel. Within just 3 rounds of user interaction on average per API method, ARBITRAR found 40 new bugs, with patches accepted for 18 of them. Moreover, ARBITRAR finds all known bugs reported by a state-of-the-art tool APISAN in a benchmark suite comprising 92 bugs with a false positive rate of only 51.5% compared to APISAN’s 87.9% 

Optimizing molecules for desired properties is a fundamental yet challenging task in chemistry, material science, and drug discovery. This paper develops a novel algorithm for optimizing molecular properties via an Expectation- Maximization (EM) like explainable evolutionary process. The algorithm is designed to mimic human experts in the process of searching for desirable molecules and alternate between two stages: the first stage on explainable local search which identifies rationales, i.e., critical subgraph patterns accounting for desired molecular properties, and the second stage on molecule completion which explores the larger space of molecules containing good rationales. We test our approach against various baselines on a real-world multi-property optimization task where each method is given the same number of queries to the property oracle. We show that our evolution-by-explanation algorithm is 79% better than the best baseline in terms of a generic metric combining aspects such as success rate, novelty, and diversity. Human expert evaluation on optimized molecules shows that 60% of top molecules obtained from our methods are deemed successful.