More Like this

1. Reproducible and accessible analysis of transposon insertion sequencing in Galaxy for qualitative essentiality analyses

   https://doi.org/10.1186/s12866-021-02184-4  

   Larivière, Delphine; Wickham, Laura; Keiler, Kenneth; Nekrutenko, Anton (December 2021, BMC Microbiology)

   null (Ed.)

   Abstract Background Significant progress has been made in advancing and standardizing tools for human genomic and biomedical research. Yet, the field of next-generation sequencing (NGS) analysis for microorganisms (including multiple pathogens) remains fragmented, lacks accessible and reusable tools, is hindered by local computational resource limitations, and does not offer widely accepted standards. One such “problem areas” is the analysis of Transposon Insertion Sequencing (TIS) data. TIS allows probing of almost the entire genome of a microorganism by introducing random insertions of transposon-derived constructs. The impact of the insertions on the survival and growth under specific conditions provides precise information about genes affecting specific phenotypic characteristics. A wide array of tools has been developed to analyze TIS data. Among the variety of options available, it is often difficult to identify which one can provide a reliable and reproducible analysis. Results Here we sought to understand the challenges and propose reliable practices for the analysis of TIS experiments. Using data from two recent TIS studies, we have developed a series of workflows that include multiple tools for data de-multiplexing, promoter sequence identification, transposon flank alignment, and read count repartition across the genome. Particular attention was paid to quality control procedures, such as determining the optimal tool parameters for the analysis and removal of contamination. Conclusions Our work provides an assessment of the currently available tools for TIS data analysis. It offers ready to use workflows that can be invoked by anyone in the world using our public Galaxy platform ( https://usegalaxy.org ). To lower the entry barriers, we have also developed interactive tutorials explaining details of TIS data analysis procedures at https://bit.ly/gxy-tis . 

   more » « less
2. Recent advances in conservation and population genomics data analysis

   https://doi.org/10.1111/eva.12659  

   Hendricks, Sarah; Anderson, Eric C.; Antao, Tiago; Bernatchez, Louis; Forester, Brenna R.; Garner, Brittany; Hand, Brian K.; Hohenlohe, Paul A.; Kardos, Martin; Koop, Ben; et al (August 2018, Evolutionary Applications)

   Abstract New computational methods and next‐generation sequencing (NGS) approaches have enabled the use of thousands or hundreds of thousands of genetic markers to address previously intractable questions. The methods and massive marker sets present both new data analysis challenges and opportunities to visualize, understand, and apply population and conservation genomic data in novel ways. The large scale and complexity of NGS data also increases the expertise and effort required to thoroughly and thoughtfully analyze and interpret data. To aid in this endeavor, a recent workshop entitled “Population Genomic Data Analysis,” also known as “ConGen 2017,” was held at the University of Montana. The ConGen workshop brought 15 instructors together with knowledge in a wide range of topics including NGS data filtering, genome assembly, genomic monitoring of effective population size, migration modeling, detecting adaptive genomic variation, genomewide association analysis, inbreeding depression, and landscape genomics. Here, we summarize the major themes of the workshop and the important take‐home points that were offered to students throughout. We emphasize increasing participation by women in population and conservation genomics as a vital step for the advancement of science. Some important themes that emerged during the workshop included the need for data visualization and its importance in finding problematic data, the effects of data filtering choices on downstream population genomic analyses, the increasing availability of whole‐genome sequencing, and the new challenges it presents. Our goal here is to help motivate and educate a worldwide audience to improve population genomic data analysis and interpretation, and thereby advance the contribution of genomics to molecular ecology, evolutionary biology, and especially to the conservation of biodiversity. 

   more » « less
3. Bayesian multi-domain learning for cancer subtype discovery from next-generation sequencing count data

   Ehsan Hajiramezanali, Siamak Zamani (December 2018, Advances in Neural Information Processing Systems 31 (NIPS 2018))

   Abstract Precision medicine aims for personalized prognosis and therapeutics by utilizing recent genome-scale high-throughput profiling techniques, including next-generation sequencing (NGS). However, translating NGS data faces several challenges. First, NGS count data are often overdispersed, requiring appropriate modeling. Second, compared to the number of involved molecules and system complexity, the number of available samples for studying complex disease, such as cancer, is often limited, especially considering disease heterogeneity. The key question is whether we may integrate available data from all different sources or domains to achieve reproducible disease prognosis based on NGS count data. In this paper, we develop a Bayesian Multi-Domain Learning (BMDL) model that derives domain-dependent latent representations of overdispersed count data based on hierarchical negative binomial factorization for accurate cancer subtyping even if the number of samples for a specific cancer type is small. Experimental results from both our simulated and NGS datasets from The Cancer Genome Atlas (TCGA) demonstrate the promising potential of BMDL for effective multi-domain learning without negative transfer effects often seen in existing multi-task learning and transfer learning methods. 

   more » « less
4. Universal annotation of the human genome through integration of over a thousand epigenomic datasets

   https://doi.org/10.1186/s13059-021-02572-z  

   Vu, Ha; Ernst, Jason (January 2022, Genome Biology)

   Abstract BackgroundGenome-wide maps of chromatin marks such as histone modifications and open chromatin sites provide valuable information for annotating the non-coding genome, including identifying regulatory elements. Computational approaches such as ChromHMM have been applied to discover and annotate chromatin states defined by combinatorial and spatial patterns of chromatin marks within the same cell type. An alternative “stacked modeling” approach was previously suggested, where chromatin states are defined jointly from datasets of multiple cell types to produce a single universal genome annotation based on all datasets. Despite its potential benefits for applications that are not specific to one cell type, such an approach was previously applied only for small-scale specialized purposes. Large-scale applications of stacked modeling have previously posed scalability challenges. ResultsUsing a version of ChromHMM enhanced for large-scale applications, we apply the stacked modeling approach to produce a universal chromatin state annotation of the human genome using over 1000 datasets from more than 100 cell types, with the learned model denoted as the full-stack model. The full-stack model states show distinct enrichments for external genomic annotations, which we use in characterizing each state. Compared to per-cell-type annotations, the full-stack annotations directly differentiate constitutive from cell type-specific activity and is more predictive of locations of external genomic annotations. ConclusionsThe full-stack ChromHMM model provides a universal chromatin state annotation of the genome and a unified global view of over 1000 datasets. We expect this to be a useful resource that complements existing per-cell-type annotations for studying the non-coding human genome. 

   more » « less
5. Using ChatGPT as a tool for training nonprogrammers to generate genomic sequence analysis code

   https://doi.org/10.1002/bmb.21899  

   Delcher, Haley A; Alsatari, Enas S; Haastrup, Adeyeye I; Naaz, Sayema; Hayes‐Guastella, Lydia A; McDaniel, Autumn M; Clark, Olivia G; Katerski, Devin M; Prinsloo, Francois O; Roberts, Olivia R; et al (May 2025, Biochemistry and Molecular Biology Education)

   Abstract Today, due to the size of many genomes and the increasingly large sizes of sequencing files, independently analyzing sequencing data is largely impossible for a biologist with little to no programming expertise. As such, biologists are typically faced with the dilemma of either having to spend a significant amount of time and effort to learn how to program themselves or having to identify (and rely on) an available computer scientist to analyze large sequence data sets. That said, the advent of AI‐powered programs like ChatGPT may offer a means of circumventing the disconnect between biologists and their analysis of genomic data critically important to their field. The work detailed herein demonstrates how implementing ChatGPT into an existing Course‐based Undergraduate Research Experience curriculum can provide a means for equipping biology students with no programming expertise the power to generate their own programs and allow those students to carry out a publishable, comprehensive analysis of real‐world Next Generation Sequencing (NGS) datasets. Relying solely on the students' biology background as a prompt for directing ChatGPT to generate Python codes, we found students could readily generate programs able to deal with and analyze NGS datasets greater than 10 gigabytes. In summary, we believe that integrating ChatGPT into education can help bridge a critical gap between biology and computer science and may prove similarly beneficial in other disciplines. Additionally, ChatGPT can provide biological researchers with powerful new tools capable of mediating NGS dataset analysis to help accelerate major new advances in the field. 

   more » « less