Biology subjects

Lapp, Z.

Publications and source records attributed to Lapp, Z..

8 recordsLinked to original sources

bioRxiv2026

wavess 1.2: Presenting an HLA-aware within-host virus sequence simulation framework

MotivationUnderstanding how virus sequences are shaped by selection can inform vaccine design and transmission inference. Modeling within-host evolution to interrogate these questions requires a detailed mechanistic framework that accurately captures sequence diversification. The CD8+ cytotoxic T-lymphocyte (CTL) response plays an important role in immune-mediated selection and can leave strong signatures in virus sequences; however, existing sequence-based within-host virus modeling frameworks do not explicitly include a human leukocyte antigen (HLA)-aware CTL response. ResultsWe extended our previously published within-host sequence evolution simulator, wavess, to include an explicit CTL response, and share a method for identifying HLA-specific CTL epitopes given a founder virus sequence. We also updated the model to permit a variable recombination rate, which allows for modeling non-adjacent genes, segmented genomes, and recombination hotspots. These extensions to wavess allow for more accurate simulation of viruses and virus genes, particularly in regions of the genome where the immune response is dominated by CTLs (rather than antibodies). It also provides the foundation for investigations of how these newly-added biological mechanisms influence within-host evolution. Availability and implementationThe core of wavess is written in Python 3, with helper functions written in R. It is available at https://github.com/MolEvolEpid/wavess.

bioinformatics↗

bioRxiv2024

Hypermut 3: Identifying specific mutational patterns in a defined nucleotide context that allows multistate characters

SummaryThe detection of APOBEC3F- and APOBEC3G-induced mutations in virus sequences is useful for identifying hypermutated sequences. These sequences are not representative of viral evolution and can therefore alter the results of downstream sequence analyses if included. We previously published the software Hypermut, which detects hypermutation events in sequences relative to a reference. Two versions of this method are available as a webtool. Neither of these methods consider multistate characters or gaps in the sequence alignment. Here, we present an updated, user-friendly web and command-line version of Hypermut with functionality to handle multistate characters and gaps in the sequence alignment. This tool allows for straightforward integration of hypermutation detection into sequence analysis pipelines. As with the previous tool, while the main purpose is to identify G to A hypermutation events, any mutational pattern and context can be specified. Availability and implementationHypermut 3 is written in Python 3. It is available as a command-line tool at https://github.com/MolEvolEpid/hypermut3 and as a webtool at https://www.hiv.lanl.gov/content/sequence/HYPERMUT/hypermutv3.html. Contacttkl@lanl.gov or seq-info@lanl.gov

bioinformatics↗

bioRxiv2022

Superinfection plays an important role in the acquisition of complex Plasmodium falciparum infections among female Anopheles mosquitoes

Studies of human malaria infections with multiple, genetically distinct parasites have illuminated mechanisms of malaria transmission. However, few studies have used the genetic diversity in mosquito infections to understand how transmission is sustained. We identified likely human sources of mosquito infections from a longitudinal cohort in Western Kenya based on genetic similarity between parasites and the timing of infections. We found that several human infections were required to reconstitute each mosquito infection and that multiple parasite clones were likely transmitted from infected humans to mosquitoes in each bite, suggesting that superinfection and co-transmission occur simultaneously and are important mechanisms of transmission. We further investigated this using an individual human and mosquito simulation model and found that co-transmission alone was unlikely to reproduce the high complexity of mosquito infections. We concluded that the superinfection of mosquitoes likely plays an important, but under studied, role in sustaining moderate to high malaria transmission.

systems biology↗

bioRxiv2022

Plasmodium falciparum genetic diversity in coincident human and mosquito hosts

Population genetic diversity of P. falciparum antigenic loci is high despite large bottlenecks in population size during the parasite life cycle. The extent of this diversity in human blood-stage infections, following expansion from a small number of liver-stage schizonts, has been well described. However, little is known about parasite genetic diversity in the vector, where a similar bottleneck and expansion occurs following parasite mating and where parasite genotypes from several different human infections may accumulate. We assessed parasite genetic diversity within human and mosquito P. falciparum infections collected from the same households during a 14-month longitudinal cohort study using amplicon deep sequencing of two antigenic gene fragments (ama1 and csp). To a prior set of infected humans (n=1175/2813; 86.2% sequencing success) and mosquito abdomens (n=199/1448; 95.5% sequencing success), we added sequences from infected mosquito heads (n=134/1448; 98.5% sequencing success). Across all sample types we observed 456 ama1 and 289 csp unique haplotypes. While both hosts contained many rare haplotypes, population genetic metrics indicated that the overall and sample-level parasite populations were more diverse in mosquitoes than in humans, and infections were more likely to harbor a dominant haplotype in humans than in mosquitoes (based on relative read abundance). Finally, within a given mosquito there was little overlap in genetic composition of abdomen and head infections, suggesting that infections may be cleared from the abdomen during a mosquitos lifespan. Taken together, our observations provide evidence for the role of the mosquito vector in maintaining sequence diversity of malaria parasite populations. Significance statementConcurrent infections with multiple strains of Plasmodium falciparum, the leading causative agent of death due to malaria, are common in highly endemic regions. During transitions within and between the parasites mosquito and human hosts, population bottlenecks occur, and distinct parasite strains may have differential fitness in the various environments encountered. These bottlenecks and fitness differences may lead to differences in strain prevalence and diversity between hosts. We investigated differences in genetic diversity between P. falciparum parasites in human and mosquito hosts and found that, compared to human parasite populations and infections, mosquito populations and infections were more diverse. This suggests that the mosquito vector may play a role in in maintaining sequence diversity in malaria parasite populations.

microbiology↗

bioRxiv2021

Teaching Python for Data Science: Collaborative development of a modular & interactive curriculum

We are bioinformatics trainees at the University of Michigan who started a local chapter of Girls Who Code to provide a fun and supportive environment for high school women to learn the power of coding. Our goal was to cover basic coding topics and data science concepts through live coding and hands-on practice. However, we could not find a resource that exactly met our needs. Therefore, over the past three years, we have developed a curriculum and instructional format using Jupyter notebooks to effectively teach introductory Python for data science. This method, inspired by The Carpentries organization, uses bite-sized lessons followed by independent practice time to reinforce coding concepts, and culminates in a data science capstone project using real-world data. We believe our open curriculum is a valuable resource to the wider education community and hope that educators will use and improve our lessons, practice problems, and teaching best practices. Anyone can contribute to our educational materials on GitHub.

scientific communication and education↗

bioRxiv2021

Developing and deploying an integrated workshop curriculum teaching computational skills for reproducible research

Inspired by well-established material and pedagogy provided by The Carpentries (Wilson 2016), we developed a two-day workshop curriculum that teaches introductory R programming for managing, analyzing, plotting and reporting data using packages from the tidyverse (Wickham et al. 2019), the Unix shell, version control with git, and GitHub. While the official Software Carpentry curriculum is comprehensive, we found that it contains too much content for a two-day workshop. We also felt that the independent nature of the lessons left learners confused about how to integrate the newly acquired programming skills in their own work. Thus, we developed a new curriculum that aims to teach novices how to implement reproducible research principles in their own data analysis. The curriculum integrates live coding lessons with individual-level and group-based practice exercises, and also serves as a succinct resource that learners can reference both during and after the workshop. Moreover, it lowers the entry barrier for new instructors as they do not have to develop their own teaching materials or sift through extensive content. We developed this curriculum during a two-day sprint, successfully used it to host a two-day virtual workshop with almost 40 participants, and updated the material based on instructor and learner feedback. We hope that our new curriculum will prove useful to future instructors interested in teaching workshops with similar learning objectives.

scientific communication and education↗

bioRxiv2020

Matchathon: A guide to student-faculty connections in PhD programs

Relevant and impactful mentors are essential to a graduate students career. Finding mentors can be challenging in umbrella programs with hundreds of faculty members. To foster connections between potential mentors and students with similar research interests, we created a Matchathon event, which has successfully enabled students to find mentors. We developed an easy-to-use R Shiny app (https://github.com/UM-OGPS/matchathon/) to facilitate matching and organizing the event that can be used at any institution. It is our hope that this resource will improve the environment and retention rates for students in the academy. The open source app is publicly available on the web (app: https://UM-OGPS.shinyapps.io/matchathon/; source code: https://github.com/UM-OGPS/matchathon/).

scientific communication and education↗

bioRxiv2019

prewas: Data pre-processing for more informative bacterial GWAS

While variant identification pipelines are becoming increasingly standardized, less attention has been paid to the pre-processing of variants prior to their use in bacterial genome-wide association studies (bGWAS). Three nuances of variant pre-processing that impact downstream identification of genetic associations include the separation of variants at multiallelic sites, separation of variants in overlapping genes, and referencing of variants relative to ancestral alleles. Here we demonstrate the importance of these variant pre-processing steps on diverse bacterial genomic datasets and present prewas, an R package, that standardizes the pre-processing of multiallelic sites, overlapping genes, and reference alleles before bGWAS. This package facilitates improved reproducibility and interpretability of bGWAS results. Prewas enables users to extract maximal information from bGWAS by implementing multi-line representation for multiallelic sites and variants in overlapping genes. Prewas outputs a binary SNP matrix that can be used for SNP-based bGWAS and will prevent the masking of minor alleles during bGWAS analysis. The optional binary gene matrix output can be used for gene-based bGWAS which will enable users to maximize the power and evolutionary interpretability of their bGWAS studies. Prewas is available for download from GitHub. DATA SUMMARYO_LIprewas is available from GitHub under the MIT License (URL: https://github.com/Snitkin-Lab-Umich/prewas) and can be installed using the command devtools::install_github("Snitkin-Lab-Umich/prewas") C_LIO_LICode to perform analyses is available from GitHub under the MIT License (URL: https://github.com/Snitkin-Lab-Umich/prewas_manuscript_analysis) C_LIO_LIAll genomes are publicly available on NCBI (see Table S1 for more details) C_LI O_TBL View this table: org.highwire.dtl.DTLVardef@137f5b6org.highwire.dtl.DTLVardef@e4a12dorg.highwire.dtl.DTLVardef@11b2a3org.highwire.dtl.DTLVardef@1e71da1org.highwire.dtl.DTLVardef@4a7286_HPS_FORMAT_FIGEXP M_TBL O_FLOATNOTable S1:C_FLOATNO O_TABLECAPTIONSources for bacterial datasets C_TABLECAPTION C_TBL IMPACT STATEMENTIn between variant calling and performing bacterial genome-wide association studies (bGWAS) there are many decisions regarding processing of variants that have the potential to impact bGWAS results. We discuss the benefits and drawbacks of various variant pre-processing decisions and present the R package prewas to standardize single nucleotide polymorphism (SNP) pre-processing, specifically to incorporate multiallelic sites and prepare the data for gene-based analyses. We demonstrate the importance of these considerations by highlighting the prevalence of multiallelic sites and SNPs in overlapping genes within diverse bacterial genomes and the impact of reference allele choice on gene-based analyses.

bioinformatics↗