Genetics and Genomics Commons^™

Cov Genome Tracker: Tracing Genomic Footprints Of Covid-19 Pandemic, Saymon Akther, Edgaras Bezrucenkovas, Brian Sulkow, Christopher Panlasigui, Li Li, Wei-Gang Qiu, Lia Di

Publications and Research

Genome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular …

Quantitative Analysis Of The Thrbcrm1-Centered Gene Regulatory Network, Benjamin Souferi, Mark M. Emerson

Publications and Research

Enhancer activity is determined by both the activity and occupancy of transcription factors as well as the specific sequences they bind. Experimental investigation of this dynamic requires the ability to manipulate components of the system, ideally in as close to an in vivo context as possible. Here we use electroporation of plasmid reporters to define critical parameters of a specific cis-regulatory element, ThrbCRM1, during retinal development. ThrbCRM1 is associated with cone photoreceptor genesis and activated in a subset of developing retinal cells that co-express the Otx2 and Onecut1 (OC1) transcription factors. Variation of reporter plasmid concentration was used to generate …

Able: Blockwise Site Frequency Spectrafor Inferring Complex Population Histories And Recombination, Champak R. Beeravolu, Michael J. Hickerson, Laurent A. F. Frantz, Konrad Lohse

Publications and Research

We introduce ABLE (Approximate Blockwise Likelihood Estimation), a novel simulation-based composite likelihood method that uses the blockwise site frequency spectrum to jointly infer past demography and recombination. ABLE is explicitly designed for a wide variety of data from unphased diploid genomes to genome-wide multi-locus data (for example, RADSeq) and can also accommodate arbitrarily large samples. We use simulations to demonstrate the accuracy of this method to infer complex histories of divergence and gene flow and reanalyze whole genome data from two species of orangutan. ABLE is available for download at https://github.com/champost/ABLE.

The Transcriptome Of The Bermuda Fireworm Odontosyllis Enopla (Annelida: Syllidae): A Unique Luciferase Gene Family And Putative Epitoky-Related Genes, Mercer R. Brugler, M. Teresa Aguado, Michael Tessler, Mark Siddall

Publications and Research

The Bermuda fireworm Odontosyllis enopla exhibits an extremely tight circalunar circadian behavior that results in an impressive bioluminescent mating swarm, thought to be due to a conventional luciferase-mediated oxidation of a light-emitting luciferin. In addition, the four eyes become hypertrophied and heavily pigmented, and the nephridial system is modified to store and release gametes and associated secretions. In an effort to elucidate transcripts related to bioluminescence, circadian or circalunar periodicity, as well as epitoky-related changes of the eyes and nephridial system, we examined the transcriptomic profile of three female O. enopladuring a bioluminescent swarm in Ferry Reach, Bermuda. …

A First Linkage Map And Downy Mildew Resistance Qtl Discovery For Sweet Basil (Ocimum Basilicum) Facilitated By Double Digestion Restriction Site Associated Dna Sequencing (Ddradseq), Robert M. Pyne, Josh Honig, Jennifer Vaiciunas, Adolfina R. Koroch, Christian Wyenandt, Stacy Bonos, James Simon

Publications and Research

Limited understanding of sweet basil (Ocimum basilicum L.) genetics and genome structure has reduced efficiency of breeding strategies. This is evidenced by the rapid, worldwide dissemination of basil downy mildew (Peronospora belbahrii) in the absence of resistant cultivars. In an effort to improve available genetic resources, expressed sequence tag simple sequence repeat (EST-SSR) and single nucleotide polymorphism (SNP) markers were developed and used to genotype the MRI x SB22 F2 mapping population, which segregates for response to downy mildew. SNP markers were generated from genomic sequences derived from double digestion restriction site associated DNA sequencing (ddRADseq). Disomic segregation was observed …

T-Dna-Genome Junctions Form Early After Infection And Are Influenced By The Chromatin State Of The Host Genome, Shay Shilo, Pooja Tripathi, Cathy Melamed Bessudo, Oren Tzfadia, Theodore R. Muth, Avraham A. Levy

Publications and Research

Agrobacterium tumefaciens mediated T-DNA integration is a common tool for plant genome manipulation. However, there is controversy regarding whether T-DNA integration is biased towards genes or randomly distributed throughout the genome. In order to address this question, we performed high-throughput mapping of T-DNA-genome junctions obtained in the absence of selection at several time points after infection. T-DNA-genome junctions were detected as early as 6 hours post-infection. T-DNA distribution was apparently uniform throughout the chromosomes, yet local biases toward AT-rich motifs and T-DNA border sequence micro-homology were detected. Analysis of the epigenetic landscape of previously isolated sites of T-DNA integration in …

Tumor Necrosis Factor Dynamically Regulates The Mrna Stabilome In Rheumatoid Arthritis Fibroblast-Like Synoviocytes, Konstantinos Loupasakis, David Kuo, Upneet K. Sokhi, Christopher Sohn, Bethany Syracuse, Eugenia G. Giannopoulou, Sung Ho Park, Hyelim Kang, Gunnar Rätsch, Lionel B. Ivashkiv, George D. Kalliolias

Publications and Research

During rheumatoid arthritis (RA), Tumor Necrosis Factor (TNF) activates fibroblast-like synoviocytes (FLS) inducing in a temporal order a constellation of genes, which perpetuate synovial inflammation. Although the molecular mechanisms regulating TNF-induced transcription are well characterized, little is known about the impact of mRNA stability on gene expression and the impact of TNF on decay rates of mRNA transcripts in FLS. To address these issues we performed RNA sequencing and genome-wide analysis of the mRNA stabilome in RA FLS. We found that TNF induces a biphasic gene expression program: initially, the inducible transcriptome consists primarily of unstable transcripts but progressively switches …

From Sexless To Sexy: Why It Is Time For Human Genetics To Consider And Report Analyses Of Sex, Matthew S. Powers, Phillip H. Smith, Sherry A. Mckee, Marissa A. Ehringer

Publications and Research

Science has come a long way with regard to the consideration of sex differences in clinical and preclinical research, but one field remains behind the curve: human statistical genetics. The goal of this commentary is to raise awareness and discussion about how to best consider and evaluate possible sex effects in the context of large-scale human genetic studies. Over the course of this commentary, we reinforce the importance of interpreting genetic results in the context of biological sex, establish evidence that sex differences are not being considered in human statistical genetics, and discuss how best to conduct and report such …

Evolutionary Interpretations Of Mycobacteriophage Biodiversity And Host-Range Through The Analysis Of Codon Usage Bias, Laura A. Esposito, Swati Gupta, Fraida Streiter, Ashley Prasad, John J. Dennehy

Publications and Research

In an genomics course sponsored by the Howard Hughes Medical Institute (HHMI), undergraduate students have isolated and sequenced the genomes of more than 1,150 mycobacteriophages, creating the largest database of sequenced bacteriophages able to infect a single host, Mycobacterium smegmatis, a soil bacterium. Genomic analysis indicates that these mycobacteriophages can be grouped into 26 clusters based on genetic similarity. These clusters span a continuum of genetic diversity, with extensive genomic mosaicism among phages in different clusters. However, little is known regarding the primary hosts of these mycobacteriophages in their natural habitats, nor of their broader host ranges. As such, it …

Machine Learning Meta-Analysis Of Large Metagenomic Datasets: Tools And Biological Insight, Edoardo Pasolli, Duy Tin Truong, Faizan Malik, Levi Waldron, Nicola Segata

Publications and Research

Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions. However, the use of such high-resolution microbial features presents new challenges, and validated computational tools for learning tasks are lacking. Moreover, classification rules have scarcely been validated in independent studies, posing questions about the generality and generalization of disease-predictive models across cohorts. In this paper, we comprehensively assess approaches to metagenomics-based prediction tasks and for quantitative assessment of the strength of potential microbiome-phenotype associations. We develop a computational framework for prediction …

Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel

Publications and Research

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of …

Cellmapper: Rapid And Accurate Inference Of Gene Expression In Difficult-To-Isolate Cell Types, Bradlee D. Nelms, Levi Waldron, Luis A. Barrera, Andrew W. Weflen, Jeremy A. Goettel, Guoji Guo, Robert K. Montgomery, Marian R. Neutra, David T. Breault, Scott B. Snapper, Stuart H. Orkin, Martha L. Bulyk, Curtis Huttenhower, Wayne I. Lencer

Publications and Research

We present a sensitive approach to predict genes expressed selectively in specific cell types, by searching publicly available expression data for genes with a similar expression profile to known cell-specific markers. Our method, CellMapper, strongly outperforms previous computational algorithms to predict cell type-specific expression, especially for rare and difficult-to-isolate cell types. Furthermore, CellMapper makes accurate predictions for human brain cell types that have never been isolated, and can be rapidly applied to diverse cell types from many tissues. We demonstrate a clinically relevant application to prioritize candidate genes in disease susceptibility loci identified by GWAS.

Phylogenomic Identification Of Regulatory Sequences In Bacteria: An Analysis Of Statistical Power And An Application To Borrelia Burgdorferi Sensu Lato, Che I. Martin, Tika Y. Sukarna, Saymon Akther, Girish Ramrattan, Pedro Pagan, Lia Di, Emmanuel F. Mongodin, Claire M. Fraser, Steven E. Schutzer, Benjamin J. Luft, Sherwood R. Casjens, Wei-Gang Qiu

Publications and Research

Phylogenomic footprinting is an approach for ab initio identification of genome-wide regulatory elements in bacterial species based on sequence conservation. The statistical power of the phylogenomic approach depends on the degree of sequence conservation, the length of regulatory elements, and the level of phylogenetic divergence among genomes. Building on an earlier model, we propose a binomial model that uses synonymous tree lengths as neutral expectations for determining the statistical significance of conserved intergenic spacer (IGS) sequences. Simulations show that the binomial model is robust to variations in the value of evolutionary parameters, including base frequencies and the transition-to-transversion ratio. We …

Improved Evidence-Based Genome-Scale Metabolic Models For Maize Leaf, Embryo, And Endosperm, Samuel M. D. Seaver, Louis M. T. Bradbury, Océane Frelin, Raphy Zarecki, Eytan Ruppin, Andrew D. Hanson, Christopher S. Henry

Publications and Research

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and …

High-Throughput Comparison, Functional Annotation, And Metabolic Modeling Of Plant Genomes Using The Plantseed Resource, Samuel M. D. Seaver, Svetlana Gerdes, Océane Frelin, Claudia Lerma-Ortiz, Louis M. T. Bradbury, Rémi Zallot, Ghulam Hasnain, Thomas D. Niehaus, Basma El Yacoubi, Shiran Pasternak, Robert Olson, Gordon Pusch, Ross Overbeek, Valérie De Crécy-Lagarde, Doreen Ware, Andrew D. Hanson, Christopher S. Henry

Publications and Research

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Collective Behaviour Without Collective Order In Wild Swarms Of Midges, Alessandro Attanasi, Andrea Cavagna, Lorenzo Del Castello, Irene Giardina, Stefania Melillo, Leonardo Parisi, Oliver Pohl, Bruno Rossaro, Edward Shen, Edmondo Silvestri, Massimilano Viale

Publications and Research

Collective behaviour is a widespread phenomenon in biology, cutting through a huge span of scales, from cell colonies up to bird flocks and fish schools. The most prominent trait of collective behaviour is the emergence of global order: individuals synchronize their states, giving the stunning impression that the group behaves as one. In many biological systems, though, it is unclear whether global order is present. A paradigmatic case is that of insect swarms, whose erratic movements seem to suggest that group formation is a mere epiphenomenon of the independent interaction of each individual with an external landmark. In these cases, …

Fast Quantitative Real-Time Pcr-Based Screening For Common Chromosomal Aneuploidies In Mouse Embryonic Stem Cells, Charlotte D'Hulst, Irena Parvanova, Delia Tomoiaga, Maria L. Sapar, Paul Feinstein

Publications and Research

Chromosomal integrity has been known for many years to affect the ability of mouse embryonic stem cells (mESCs) to contribute to the germline of chimeric mice. Abnormal chromosomes are generally detected by standard cytogenetic karyotyping. However, this method is expensive, time consuming, and often omitted prior to blastocyst injection, consequently reducing the frequency of mESC-derived offspring. Here, we show a fast, accurate, and inexpensive screen for identifying the two most common aneuploidies (Trisomy 8 and loss of chromosome Y) in genetically manipulated mESCs using quantitative real-time PCR (qPCR). Screening against these two aneuploidies significantly increases the fraction of normal mESC …

Signatures Of Rapid Evolution In Urban And Rural Transcriptomes Of White-Footed Mice (Peromyscus Leucopus) In The New York Metropolitan Area, Stephen Edward Harris, Jason Munshi-South, Craig Oberfell, Rachel O'Neill

Publications and Research

Urbanization is a major cause of ecological degradation around the world, and human settlement in large cities is accelerating. New York City (NYC) is one of the oldest and most urbanized cities in North America, but still maintains 20% vegetation cover and substantial populations of some native wildlife. The white-footed mouse, Peromyscus leucopus, is a common resident of NYC’s forest fragments and an emerging model system for examining the evolutionary consequences of urbanization. In this study, we developed transcriptomic resources for urban P. leucopus to examine evolutionary changes in protein-coding regions for an exemplar “urban adapter.” We used Roche 454 …

Genome-Wide Analyses Of Shavenbaby Target Genes Reveals Distinct Features Of Enhancer Organization, Delphine Menoret, Marc Santolini, Isabelle Fernandes, Rebecca Spokony, Jennifer Zanet, Ignacio Gonzalez, Yvan Latapie, Pierre Ferrer, Hervé Rouault, Kevin P. White, Philippe Besse, Vincent Hakim, Stein Aerts, Francois Payre, Serge Plaza

Publications and Research

Background: Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes.

Results: We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome …

Pten Regulation Of Local And Long-Range Connections In Mouse Auditory Cortex, Qiaojie Xiong, Hysell V. Oviedo, Lloyd C. Trotman, Anthony M. Zador

Publications and Research

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed …

Comparative Genomics Of The Pathogenic Ciliate Ichthyophthirius Multifiliis, Its Free-Living Relatives And A Host Species Provide Insights Into Adoption Of A Parasitic Lifestyle And Prospects For Disease Control, Robert S. Coyne, Linda Hannick, Dhanasekaran Shanmugam, Jessica B. Hostetler, Daniel Brami, Vinita S. Joardar, Justin Johnson, Diana Radune, Irtisha Singh, Jonathan H. Badger, Ujjwal Kumar, Milton Saier, Yufeng Wang, Hong Cai, Jianying Gu, Michael W. Mather, Akhil B. Vaidya, David E. Wilkes, Vidyalakshmi Rajagopalan, David J. Asai, Chad G. Pearson, Robert C. Findly, Harry W. Dickerson, Martin Wu, Cindy Martens, Yves Van De Peer, David S. Roos, Donna M. Cassidy-Hanley, Theodore G. Clark

Publications and Research

Background

Ichthyophthirius multifiliis, commonly known as Ich, is a highly pathogenic ciliate responsible for 'white spot', a disease causing significant economic losses to the global aquaculture industry. Options for disease control are extremely limited, and Ich's obligate parasitic lifestyle makes experimental studies challenging. Unlike most well-studied protozoan parasites, Ich belongs to a phylum composed primarily of free-living members. Indeed, it is closely related to the model organism Tetrahymena thermophila. Genomic studies represent a promising strategy to reduce the impact of this disease and to understand the evolutionary transition to parasitism.

Results

We report the sequencing, assembly and annotation …