Lee Zamparo

Here we present HiC-DC, a principled method to estimate the statistical significance (P values) of chromatin interactions from Hi-C experiments. HiC-DC uses hurdle negative binomial regression account for systematic sources of variation in Hi-C read counts-for example, distance-dependent random polymer ligation and GC content and mappability bias-and model zero inflation and overdispersion. Applied to high-resolution Hi-C data in a lymphoblastoid cell line, HiC-DC detects significant interactions at the sub-topologically associating domain level, identifying potential structural and regulatory interactions supported by CTCF binding sites, DNase accessibility, and/or active histone marks. CTCF-associated interactions are most strongly enriched in the middle genomic distance range (∼700 kb-1.5 Mb), while interactions involving actively marked DNase accessible elements are enriched both at short (<500 kb) and longer (>1.5 Mb) genomic distances. There is a striking enrichment of longer-range interactions connecting replication-dependent histone genes on chromosome 6, potentially representing the chromatin architecture at the histone locus body.

Explainability for machine learning models has gained considerable attention within the research community given the importance of deploying more reliable machine-learning systems. In computer vision applications, generative counterfactual methods indicate how to perturb a model’s input to change its prediction, providing details about the model’s decision-making. Current methods tend to generate trivial counterfactuals about a model’s decisions, as they often suggest to exaggerate or remove the presence of the attribute being classified. For the machine learning practitioner, these types of counterfactuals offer little value, since they provide no new information about undesired model or data biases. In this work, we identify the problem of trivial counterfactual generation and we propose DiVE to alleviate it. DiVE learns a perturbation in a disentangled latent space that is constrained using a diversity-enforcing loss to uncover multiple valuable explanations about the model’s prediction. Further, we introduce a mechanism to prevent the model from producing trivial explanations. Experiments on CelebA and Synbols demonstrate that our model improves the success rate of producing high-quality valuable explanations when compared to previous state-of-the-art methods. Code is available at https://github.com/ElementAI/beyond-trivial-explanations.