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1. Liftoff: an accurate gene annotation mapping tool

   https://doi.org/10.1101/2020.06.24.169680  

   Shumate, A. ; Salzberg, S.L. ( June 2020 , bioRxiv)

   Improvements in DNA sequencing technology and computational methods have led to a substantial increase in the creation of high-quality genome assemblies of many species. To understand the biology of these genomes, annotation of gene features and other functional elements is essential; however for most species, only the reference genome is well-annotated. One strategy to annotate new or improved genome assemblies is to map or ‘lift over’ the genes from a previously-annotated reference genome. Here we describe Liftoff, a new genome annotation lift-over tool capable of mapping genes between two assemblies of the same or closely-related species. Liftoff aligns genes from a reference genome to a target genome and finds the mapping that maximizes sequence identity while preserving the structure of each exon, transcript, and gene. We show that Liftoff can accurately map 99.9% of genes between two versions of the human reference genome with an average sequence identity >99.9%. We also show that Liftoff can map genes across species by successfully lifting over 98.4% of human protein-coding genes to a chimpanzee genome assembly with 98.7% sequence identity. Availability The source code for Liftoff is available at https://github.com/agshumate/Liftoff 

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2. Liftoff: accurate mapping of gene annotations

   https://doi.org/10.1093/bioinformatics/btaa1016  

   Shumate, Alaina ; Salzberg, Steven L ( May 2021 , Bioinformatics)

   Valencia, Alfonso (Ed.)

   Abstract Motivation Improvements in DNA sequencing technology and computational methods have led to a substantial increase in the creation of high-quality genome assemblies of many species. To understand the biology of these genomes, annotation of gene features and other functional elements is essential; however, for most species, only the reference genome is well-annotated. Results One strategy to annotate new or improved genome assemblies is to map or ‘lift over’ the genes from a previously annotated reference genome. Here, we describe Liftoff, a new genome annotation lift-over tool capable of mapping genes between two assemblies of the same or closely related species. Liftoff aligns genes from a reference genome to a target genome and finds the mapping that maximizes sequence identity while preserving the structure of each exon, transcript and gene. We show that Liftoff can accurately map 99.9% of genes between two versions of the human reference genome with an average sequence identity >99.9%. We also show that Liftoff can map genes across species by successfully lifting over 98.3% of human protein-coding genes to a chimpanzee genome assembly with 98.2% sequence identity. Availability and implementation Liftoff can be installed via bioconda and PyPI. In addition, the source code for Liftoff is available at https://github.com/agshumate/Liftoff. Supplementary information Supplementary data are available at Bioinformatics online. 

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3. Somatic genome architecture and molecular evolution are decoupled in “young” linage-specific gene families in ciliates

   https://doi.org/10.1371/journal.pone.0291688  

   Maurer-Alcalá, Xyrus X ; Cote-L’Heureux, Auden ; Kosakovsky_Pond, Sergei L ; Katz, Laura A ( January 2024 , PLOS ONE)

   Schmidt, Edward E (Ed.)

   The evolution of lineage-specific gene families remains poorly studied across the eukaryotic tree of life, with most analyses focusing on the recent evolution ofde novogenes in model species. Here we explore the origins of lineage-specific genes in ciliates, a ~1 billion year old clade of microeukaryotes that are defined by their division of somatic and germline functions into distinct nuclei. Previous analyses on conserved gene families have shown the effect of ciliates’ unusual genome architecture on gene family evolution: extensive genome processing–the generation of thousands of gene-sized somatic chromosomes from canonical germline chromosomes–is associated with larger and more diverse gene families. To further study the relationship between ciliate genome architecture and gene family evolution, we analyzed lineage specific gene families from a set of 46 transcriptomes and 12 genomes representing x species from eight ciliate classes. We assess how the evolution lineage-specific gene families occurs among four groups of ciliates: extensive fragmenters with gene-size somatic chromosomes, non-extensive fragmenters with “large’’ multi-gene somatic chromosomes, Heterotrichea with highly polyploid somatic genomes and Karyorelictea with ‘paradiploid’ somatic genomes. Our analyses demonstrate that: 1) most lineage-specific gene families are found at shallow taxonomic scales; 2) extensive genome processing (i.e., gene unscrambling) during development likely influences the size and number of young lineage-specific gene families; and 3) the influence of somatic genome architecture on molecular evolution is increasingly apparent in older gene families. Altogether, these data highlight the influences of genome architecture on the evolution of lineage-specific gene families in eukaryotes.

    

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4. Detecting patterns of accessory genome coevolution in Staphylococcus aureus using data from thousands of genomes

   https://doi.org/10.1186/s12859-023-05363-4  

   Mehta, Rohan S. ; Petit, III, Robert A. ; Read, Timothy D. ; Weissman, Daniel B. ( June 2023 , BMC Bioinformatics)

   Bacterial genomes exhibit widespread horizontal gene transfer, resulting in highly variable genome content that complicates the inference of genetic interactions. In this study, we develop a method for detecting coevolving genes from large datasets of bacterial genomes based on pairwise comparisons of closely related individuals, analogous to a pedigree study in eukaryotic populations. We apply our method to pairs of genes from theStaphylococcus aureusaccessory genome of over 75,000 annotated gene families using a database of over 40,000 whole genomes. We find many pairs of genes that appear to be gained or lost in a coordinated manner, as well as pairs where the gain of one gene is associated with the loss of the other. These pairs form networks of rapidly coevolving genes, primarily consisting of genes involved in virulence, mechanisms of horizontal gene transfer, and antibiotic resistance, particularly the SCCmeccomplex. While we focus on gene gain and loss, our method can also detect genes that tend to acquire substitutions in tandem, or genotype-phenotype or phenotype-phenotype coevolution. Finally, we present the R package that allows for the computation of our method.

    

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5. The first gapless, reference-quality, fully annotated genome from a Southern Han Chinese individual

   https://doi.org/10.1093/g3journal/jkac321  

   Chao, Kuan-Hao ; Zimin, Aleksey V. ; Pertea, Mihaela ; Salzberg, Steven L. ; Emerson, ed., J. J. ( January 2023 , G3: Genes, Genomes, Genetics)

   We used long-read DNA sequencing to assemble the genome of a Southern Han Chinese male. We organized the sequence into chromosomes and filled in gaps using the recently completed T2T-CHM13 genome as a guide, yielding a gap-free genome, Han1, containing 3,099,707,698 bases. Using the T2T-CHM13 annotation as a reference, we mapped all genes onto the Han1 genome and identified additional gene copies, generating a total of 60,708 putative genes, of which 20,003 are protein-coding. A comprehensive comparison between the genes revealed that 235 protein-coding genes were substantially different between the individuals, with frameshifts or truncations affecting the protein-coding sequence. Most of these were heterozygous variants in which one gene copy was unaffected. This represents the first gene-level comparison between two finished, annotated individual human genomes.

    

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