Saurabh Sinha

Payam Dibaeinia, Saurabh Sinha

The discovery of causal relationships from high-dimensional data is a major open problem in bioinformatics. Machine learning and feature attribution models have shown great promise in this context but lack causal interpretation. Here, we show that a popular feature attribution model estimates a causal quantity reflecting the influence of one variable on another, under certain assumptions. We leverage this insight to implement a new tool, CIMLA, for discovering condition-dependent changes in causal relationships. We then use CIMLA to identify differences in gene regulatory networks between biological conditions, a problem that has received great attention in recent years. Using extensive benchmarking on simulated data sets, we show that CIMLA is more robust to confounding variables and is more accurate than leading methods. Finally, we employ CIMLA to analyze a previously published single-cell RNA-seq data set collected from subjects with and without Alzheimer's disease (AD), discovering several potential regulators of AD.

Saba Ghaffari, Ehsan Saleh, Alexander G. Schwing et al.

Protein design, a grand challenge of the day, involves optimization on a fitness landscape, and leading methods adopt a model-based approach where a model is trained on a training set (protein sequences and fitness) and proposes candidates to explore next. These methods are challenged by sparsity of high-fitness samples in the training set, a problem that has been in the literature. A less recognized but equally important problem stems from the distribution of training samples in the design space: leading methods are not designed for scenarios where the desired optimum is in a region that is not only poorly represented in training data, but also relatively far from the highly represented low-fitness regions. We show that this problem of "separation" in the design space is a significant bottleneck in existing model-based optimization tools and propose a new approach that uses a novel VAE as its search model to overcome the problem. We demonstrate its advantage over prior methods in robustly finding improved samples, regardless of the imbalance and separation between low- and high-fitness samples. Our comprehensive benchmark on real and semi-synthetic protein datasets as well as solution design for physics-informed neural networks, showcases the generality of our approach in discrete and continuous design spaces. Our implementation is available at https://github.com/sabagh1994/PGVAE.

Faraz Faghri, Sayed Hadi Hashemi, Mohammad Babaeizadeh et al.

In an effort to overcome the data deluge in computational biology and bioinformatics and to facilitate bioinformatics research in the era of big data, we identify some of the most influential algorithms that have been widely used in the bioinformatics community. These top data mining and machine learning algorithms cover classification, clustering, regression, graphical model-based learning, and dimensionality reduction. The goal of this study is to guide the focus of scalable computing experts in the endeavor of applying new storage and scalable computation designs to bioinformatics algorithms that merit their attention most, following the engineering maxim of "optimize the common case".