Programming by Examples (PBE) has the potential to revolutionize end-user programming by enabling end users, most of whom are non-programmers, to create small scripts for automating repetitive tasks. However, examples, though often easy to provide, are an ambiguous specification of the user's intent. Because of that, a key impedance in adoption of PBE systems is the lack of user confidence in the correctness of the program that was synthesized by the system. We present two novel user interaction models that communicate actionable information to the user to help resolve ambiguity in the examples. One of these models allows the user to effectively navigate between the huge set of programs that are consistent with the examples provided by the user. The other model uses active learning to ask directed example-based questions to the user on the test input data over which the user intends to run the synthesized program. Our user studies show that each of these models significantly reduces the number of errors in the performed task without any difference in completion time. Moreover, both models are perceived as useful, and the proactive active-learning based model has a slightly higher preference regarding the users' confidence in the result.

We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each gene is perturbed—having distinct regulator connectivity in the inferred gene-regulator dependencies between the disease and normal conditions. This approach has distinct advantages over existing methods. First, DISCERN infers conditional dependencies between candidate regulators and genes, where conditional dependence relationships discriminate the evidence for direct interactions from indirect interactions more precisely than pairwise correlation. Second, DISCERN uses a new likelihood-based scoring function to alleviate concerns about accuracy of the specific edges inferred in a particular network. DISCERN identifies perturbed genes more accurately in synthetic data than existing methods to identify perturbed genes between distinct states. In expression datasets from patients with acute myeloid leukemia (AML), breast cancer and lung cancer, genes with high DISCERN scores in each cancer are enriched for known tumor drivers, genes associated with the biological processes known to be important in the disease, and genes associated with patient prognosis, in the respective cancer. Finally, we show that DISCERN can uncover potential mechanisms underlying network perturbation by explaining observed epigenomic activity patterns in cancer and normal tissue types more accurately than alternative methods, based on the available epigenomic data from the ENCODE project.

A main problem with reproducing machine learning publications is the variance of metric implementations across papers. A lack of standardization leads to different behavior in mechanisms such as checkpointing, learning rate schedulers or early stopping, that will influence the reported results. For example, a complex metric such as Fréchet inception distance (FID) for synthetic image quality evaluation (Heusel et al., 2017) will differ based on the specific interpolation method used.

We present a computational framework, called DISCERN (DIfferential SparsE Regulatory Network), to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states. DISCERN takes two expression datasets as input: an expression dataset of diseased tissues from patients with a disease of interest and another expression dataset from matching normal tissues. DISCERN estimates the extent to which each gene is perturbed-having distinct regulator connectivity in the inferred gene-regulator dependencies between the disease and normal conditions. This approach has distinct advantages over existing methods. First, DISCERN infers conditional dependencies between candidate regulators and genes, where conditional dependence relationships discriminate the evidence for direct interactions from indirect interactions more precisely than pairwise correlation. Second, DISCERN uses a new likelihood-based scoring function to alleviate concerns about accuracy of the specific edges inferred in a particular network. DISCERN identifies perturbed genes more accurately in synthetic data than existing methods to identify perturbed genes between distinct states. In expression datasets from patients with acute myeloid leukemia (AML), breast cancer and lung cancer, genes with high DISCERN scores in each cancer are enriched for known tumor drivers, genes associated with the biological processes known to be important in the disease, and genes associated with patient prognosis, in the respective cancer. Finally, we show that DISCERN can uncover potential mechanisms underlying network perturbation by explaining observed epigenomic activity patterns in cancer and normal tissue types more accurately than alternative methods, based on the available epigenomic data from the ENCODE project. Author SummaryCertain genes can regulate other genes' expression and activity levels to perform key biological processes in a cell. Understanding how genes affect expression levels among one another is a fundamental goal in molecular biology. New statistical techniques that analyze genome-wide mRNA expression data obtained from different individuals can improve our PLOS Computational Biology |