Data generation and network reconstruction strategies for single cell transcriptomic profiles of CRISPR-mediated gene perturbations.

Recent advances in single-cell RNA-sequencing (scRNA-seq) in combination with CRISPR/Cas9 technologies have enabled the development of methods for large-scale perturbation studies with transcriptional readouts. These methods are highly scalable and have the potential to provide a wealth of information on the biological networks that underlie cellular response. Here we discuss how to overcome several key challenges to generate and analyse data for the confident reconstruction of models of the underlying cellular network. Some challenges are generic, and apply to analysing any single-cell transcriptomic data, while others are specific to combined single-cell CRISPR/Cas9 data, in particular barcode swapping, knockdown efficiency, multiplicity of infection and potential confounding factors. We also provide a curated collection of published data sets to aid the development of analysis strategies. Finally, we discuss several network reconstruction approaches, including co-expression networks and Bayesian networks, as well as their limitations, and highlight the potential of Nested Effects Models for network reconstruction from scRNA-seq data. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.

A Guide to Dictionary-Based Text Mining.

PubMed contains more than 27 million documents, and this number is growing at an estimated 4% per year. Even within specialized topics, it is no longer possible for a researcher to read any field in its entirety, and thus nobody has a complete picture of the scientific knowledge in any given field at any time. Text mining provides a means to automatically read this corpus and to extract the relations found therein as structured information. Having data in a structured format is a huge boon for computational efforts to access, cross reference, and mine the data stored therein. This is increasingly useful as biological research is becoming more focused on systems and multi-omics integration. This chapter provides an overview of the steps that are required for text mining: tokenization, named entity recognition, normalization, event extraction, and benchmarking. It discusses a variety of approaches to these tasks and then goes into detail on how to prepare data for use specifically with the JensenLab tagger. This software uses a dictionary-based approach and provides the text mining evidence for STRING and several other databases.

An Integrative Approach to Virus-Host Protein-Protein Interactions.

Since cell regulation and protein expression can be dramatically altered upon infection by viruses, studying the mechanisms by which viruses infect cells and the regulatory networks they disrupt is essential to understanding viral pathogenicity. This line of study can also lead to discoveries about the workings of host cells themselves. Computational methods are rapidly being developed to investigate viral-host interactions, and here we highlight recent methods and the insights that they have revealed so far, with a particular focus on methods that integrate different types of data. We also review the challenges of working with viruses compared with traditional cellular biology, and the limitations of current experimental and informatics methods.

miRandola 2017: a curated knowledge base of non-invasive biomarkers.

miRandola (http://mirandola.iit.cnr.it/) is a database of extracellular non-coding RNAs (ncRNAs) that was initially published in 2012, foreseeing the relevance of ncRNAs as non-invasive biomarkers. An increasing amount of experimental evidence shows that ncRNAs are frequently dysregulated in diseases. Further, ncRNAs have been discovered in different extracellular forms, such as exosomes, which circulate in human body fluids. Thus, miRandola 2017 is an effort to update and collect the accumulating information on extracellular ncRNAs that is spread across scientific publications and different databases. Data are manually curated from 314 articles that describe miRNAs, long non-coding RNAs and circular RNAs. Fourteen organisms are now included in the database, and associations of ncRNAs with 25 drugs, 47 sample types and 197 diseases. miRandola also classifies extracellular RNAs based on their extracellular form: Argonaute2 protein, exosome, microvesicle, microparticle, membrane vesicle, high density lipoprotein and circulating. We also implemented a new web interface to improve the user experience.