SUMMARY: The emergence of multiomic single-cell Hi-C (scHi-C) methods, which simultaneously profile chromatin conformation and other modalities such as gene expression or DNA methylation, creates tremendous opportunities for studying the genome's structure-function relationships. Existing tools for processing multiomic scHi-C datasets lack certain key functions for downstream bioinformatics analysis. We present map3C, a software tool that incorporates additional key functions. Specifically, we demonstrate that map3C facilitates multiomic scHi-C processing, quality control, and identification of structural variant locations in the genome. AVAILABILITY AND IMPLEMENTATION: map3C is available at https://github.com/luogenomics/map3C and is archived at https://doi.org/10.5281/zenodo.20724719.

MOTIVATION: Identifying pairwise associations between genomic loci is an important challenge for which large and diverse collections of epigenomic and transcription factor (TF) binding data can potentially be informative. RESULTS: We developed Learning Evidence of Pairwise Association from Epigenomic and TF binding data (LEPAE). LEPAE uses neural networks to quantify evidence of association for pairs of genomic windows from large-scale epigenomic and TF binding data along with distance information. We applied LEPAE using thousands of human datasets. We show using additional data that LEPAE captures biologically meaningful pairwise relationships between genomic loci, and we expect LEPAE scores to be a resource. AVAILABILITY AND IMPLEMENTATION: The LEPAE scores and the software are available at https://github.com/ernstlab/LEPAE.

Developing scalable and robust routing protocols for Mobile ad hoc Networks (MANETs) can be challenging given issues related to limited energy, node mobility, and changing topology. While a variety of MANET routing protocols are available, they are often hindered by node mobility. Artificial Intelligence (AI) approaches (i.e. biologically inspired and machine learning algorithms) provide a novel approach to MANET routing problems that are better equipped to address these issues. These approaches can improve network performance by minimizing energy consumption, improving overhead, and more. This paper’s main contribution is that it promotes the use of AI to provide high-performance routing protocols. Our work surveys both biologically inspired and machine learning approaches and discusses the contributions made to provide readers with a greater understanding of these approaches and methods that can be taken to improve routing and other performance metrics.

MOTIVATION: Genome-wide maps of epigenetic modifications are powerful resources for non-coding genome annotation. Maps of multiple epigenetics marks have been integrated into cell or tissue type-specific chromatin state annotations for many cell or tissue types. With the increasing availability of multiple chromatin state maps for biologically similar samples, there is a need for methods that can effectively summarize the information about chromatin state annotations within groups of samples and identify differences across groups of samples at a high resolution. RESULTS: We developed CSREP, which takes as input chromatin state annotations for a group of samples. CSREP then probabilistically estimates the state at each genomic position and derives a representative chromatin state map for the group. CSREP uses an ensemble of multi-class logistic regression classifiers that predict the chromatin state assignment of each sample given the state maps from all other samples. The difference in CSREP's probability assignments for the two groups can be used to identify genomic locations with differential chromatin state assignments. Using groups of chromatin state maps of a diverse set of cell and tissue types, we demonstrate the advantages of using CSREP to summarize chromatin state maps and identify biologically relevant differences between groups at a high resolution. AVAILABILITY AND IMPLEMENTATION: The CSREP source code and generated data are available at http://github.com/ernstlab/csrep. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In recent years, methods were proposed for assigning feature importance scores to measure the contribution of individual features. While in some cases the goal is to understand a specific model, in many cases the goal is to understand the contribution of certain properties (features) to a real-world phenomenon. Thus, a distinction has been made between feature importance scores that explain a model and scores that explain the data. When explaining the data, machine learning models are used as proxies in settings where conducting many real-world experiments is expensive or prohibited. While existing feature importance scores show great success in explaining models, we demonstrate their limitations when explaining the data, especially in the presence of correlations between features. Therefore, we develop a set of axioms to capture properties expected from a feature importance score when explaining data and prove that there exists only one score that satisfies all of them, the Marginal Contribution Feature Importance (MCI). We analyze the theoretical properties of this score function and demonstrate its merits empirically.

Inequitable access to telecommunication networks is having discernible impacts on Canadians, particularly in Northern and remote communities. More complete, available, and interoperable datasets are needed to better quantify inequitable access, particularly at the ‘last mile’ of the internet. Community-based internet assessment initiatives have been recognized as valuable programs in this pursuit. The Rigolet Internet Assessment Initiative (RIAI) is a project located in and led by the Inuit of Rigolet, Nunatsiavut, to measure and better understand the community’s telecommunications environment. The RIAI data collection began in 2019 and involves collecting measurements every twenty minutes from ten participating households. Using participatory design methods, this paper describes the co-creation of the initiative, the design of the system and development of the software suite, deployment of the integrated hardware tools, and analysis of a sample of the resulting dataset. As a result of this work, an additional 9,436 measurements were added to databases of publicly available download and upload speeds for the community of Rigolet (where only 2 existed prior) where they can be used to support data-driven policy. Further, findings indicate that the quality of internet in Rigolet is far below the Canadian Radio and Telecommunications Commission’s upload and download speed goals.

MOTIVATION: Chromatin interactions play an important role in genome architecture and gene regulation. The Hi-C assay generates such interactions maps genome-wide, but at relatively low resolutions (e.g. 5-25 kb), which is substantially coarser than the resolution of transcription factor binding sites or open chromatin sites that are potential sources of such interactions. RESULTS: To predict the sources of Hi-C-identified interactions at a high resolution (e.g. 100 bp), we developed a computational method that integrates data from DNase-seq and ChIP-seq of TFs and histone marks. Our method, χ-CNN, uses this data to first train a convolutional neural network (CNN) to discriminate between called Hi-C interactions and non-interactions. χ-CNN then predicts the high-resolution source of each Hi-C interaction using a feature attribution method. We show these predictions recover original Hi-C peaks after extending them to be coarser. We also show χ-CNN predictions enrich for evolutionarily conserved bases, eQTLs and CTCF motifs, supporting their biological significance. χ-CNN provides an approach for analyzing important aspects of genome architecture and gene regulation at a higher resolution than previously possible. AVAILABILITY AND IMPLEMENTATION: χ-CNN software is available on GitHub (https://github.com/ernstlab/X-CNN). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Expression quantitative trait loci (eQTLs) are genetic variants that affect gene expression. In eQTL studies, one important task is to find eGenes or genes whose expressions are associated with at least one eQTL. The standard statistical method to determine whether a gene is an eGene requires association testing at all nearby variants and the permutation test to correct for multiple testing. The standard method however does not consider genomic annotation of the variants. In practice, variants near gene transcription start sites (TSSs) or certain histone modifications are likely to regulate gene expression. In this article, we introduce a novel eGene detection method that considers this empirical evidence and thereby increases the statistical power. RESULTS: We applied our method to the liver Genotype-Tissue Expression (GTEx) data using distance from TSSs, DNase hypersensitivity sites, and six histone modifications as the genomic annotations for the variants. Each of these annotations helped us detected more candidate eGenes. Distance from TSS appears to be the most important annotation; specifically, using this annotation, our method discovered 50% more candidate eGenes than the standard permutation method. CONTACT: [email protected] or [email protected].

Transcriptional enhancers play critical roles in regulation of gene expression, but their identification in the eukaryotic genome has been challenging. Recently, it was shown that enhancers in the mammalian genome are associated with characteristic histone modification patterns, which have been increasingly exploited for enhancer identification. However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction.

A Customized Reconfigurable Interconnection Network (CRIN) refers to a minimal switching network, yielding routing solutions for any element in a pre-given set of routing requirements. The CRIN design problem looks for the best performance and resource-flexibility trade-off between two extreme design contexts ASIC and FPGA. In this paper we give the modeling of this problem for both directed and undirected interconnections. A heuristic algorithm for automatic generation of CRIN is proposed along with its experimental justifications. This study was motivated from the design of reconfigurable systems-on-a-chip for multiple applications.

While Escherichia coli has one of the most comprehensive datasets of experimentally verified transcriptional regulatory interactions of any organism, it is still far from complete. This presents a problem when trying to combine gene expression and regulatory interactions to model transcriptional regulatory networks. Using the available regulatory interactions to predict new interactions may lead to better coverage and more accurate models. Here, we develop SEREND (SEmi-supervised REgulatory Network Discoverer), a semi-supervised learning method that uses a curated database of verified transcriptional factor-gene interactions, DNA sequence binding motifs, and a compendium of gene expression data in order to make thousands of new predictions about transcription factor-gene interactions, including whether the transcription factor activates or represses the gene. Using genome-wide binding datasets for several transcription factors, we demonstrate that our semi-supervised classification strategy improves the prediction of targets for a given transcription factor. To further demonstrate the utility of our inferred interactions, we generated a new microarray gene expression dataset for the aerobic to anaerobic shift response in E. coli. We used our inferred interactions with the verified interactions to reconstruct a dynamic regulatory network for this response. The network reconstructed when using our inferred interactions was better able to correctly identify known regulators and suggested additional activators and repressors as having important roles during the aerobic-anaerobic shift interface.

BACKGROUND: Time series microarray experiments are widely used to study dynamical biological processes. Due to the cost of microarray experiments, and also in some cases the limited availability of biological material, about 80% of microarray time series experiments are short (3-8 time points). Previously short time series gene expression data has been mainly analyzed using more general gene expression analysis tools not designed for the unique challenges and opportunities inherent in short time series gene expression data. RESULTS: We introduce the Short Time-series Expression Miner (STEM) the first software program specifically designed for the analysis of short time series microarray gene expression data. STEM implements unique methods to cluster, compare, and visualize such data. STEM also supports efficient and statistically rigorous biological interpretations of short time series data through its integration with the Gene Ontology. CONCLUSION: The unique algorithms STEM implements to cluster and compare short time series gene expression data combined with its visualization capabilities and integration with the Gene Ontology should make STEM useful in the analysis of data from a significant portion of all microarray studies. STEM is available for download for free to academic and non-profit users at http://www.cs.cmu.edu/~jernst/stem.