Biology subjects

Copetti, D.

Publications and source records attributed to Copetti, D..

At least 19 recordsLinked to original sources

bioRxiv2025

Candidate genes for stem rust resistance in Italian ryegrass revealed by nested association mapping

Stem rust, caused by Puccinia graminis ssp. graminicola, is a major disease affecting the outcrossing species Italian ryegrass (Lolium multiflorum Lam.), leading to substantial reductions in seed yield. Until now, knowledge on the genetic control of stem rust resistance in Italian ryegrass has been limited to a few quantitative trait loci identified in bi-parental mapping populations. To discover novel resistance sources for use in breeding programs, appropriate plant populations, reliable phenotyping methods and advanced genomic tools are essential. In this study, we utilized a previously established F2 nested association mapping (NAM) population comprising 708 individuals derived from 24 founder plants exhibiting high variation in stem rust resistance. Phenotypic evaluation was conducted under natural inoculation in three location-by-year combinations. By integrating reduced-representation sequencing of the NAM population with whole-genome sequencing of the founder plants, we identified 3,199,253 SNP markers for association mapping. The high SNP marker density, together with the strong detection power of the NAM population, enabled the identification of four novel candidate genes. Two of these genes, located on chromosomes 6 and 7, encode receptor-like serine/threonine kinases that are known to play a role in stem rust resistance in other crops. Within the serine/threonine kinase gene Chr7.32208, two superior haplotypes were identified that can be directly implemented as selection criteria in breeding programs. The novel stem rust resistance candidate genes reported here provide promising targets for functional validation and the improvement of stem rust resistance in Italian ryegrass breeding. Key messageField phenotyping of a previously established NAM population for stem rust resistance, combined with high-density genotyping, enabled the identification of novel sources of stem rust resistance in Italian ryegrass.

plant biology↗

bioRxiv2025

The first nested association mapping (NAM) population for outbreeding Italian ryegrass reveals candidate genes for seed shattering and related traits

Nested association mapping (NAM) populations are a powerful tool for investigating the genetic control of agronomically important traits and have been successfully used in many inbreeding crops. Here, we present the first NAM population established in an outcrossing forage grass species, Italian ryegrass (Lolium multiflorum Lam.), to dissect the genetic control of seed shattering. The NAM population was based on 23 diverse and one common founder plants and consisted of 708 F2 individuals. Reduced-representation sequencing (ddRAD) of the 708 F2 individuals, combined with whole genome sequencing data of the 24 founder plants, yielded a total of 3,199,253 SNPs that were used for population structure analysis, parentship analysis and genome-wide association studies. Phenotypic data for seed shattering and seed yield-related traits, collected in three year x location environments, showed high phenotypic variance within the NAM population. A total of seven QTL were identified for seed shattering, seed yield, spike length, flag leaf length and flowering time. Within these QTL regions, one candidate gene for seed shattering and three candidate genes for flowering time were identified. For seed shattering, the significant SNP association within the gene chr7.26897, known to be in involved in ripening-related pathways, explained 10.03% of the phenotypic variance. These candidate genes identified provide valuable targets for functional validation and demonstrate the effectiveness of NAM populations for elucidating the genetic architecture of complex traits in outcrossing forage grasses.

plant biology↗

bioRxiv2025

A pan-gene catalogue of Asian cultivated rice

The rice genome underpins fundamental research and breeding, but the Nipponbare (japonica) reference does not fully encompass the genetic diversity of Asian rice. To address this gap, the Rice Population Reference Panel (RPRP) was developed, comprising high-quality assemblies of 16 rice cultivars to represent japonica, indica, aus, and aromatic varietal groups. The RPRP has been consistently annotated, supported by extensive experimental data and here we report the computational assignment, characterization and dissemination of stably identified pan-genes. We identified 25,178 core pan-genes shared across all cultivars, alongside cultivar-specific and family-enriched genes. Core genes exhibit higher gene expression and proteomic evidence, higher confidence protein domains and AlphaFold structures, while cultivar-specific genes were enriched for domains under selective breeding pressure, such as for disease resistance. This resource, integrated into public databases, enables researchers to explore genetic and functional diversity via a population-aware "reference guide" across rice genomes, advancing both basic and applied research.

genomics↗

bioRxiv2025

Universal orthologs infer deep phylogenies and improve genome quality assessments

Universal single-copy orthologs are the most conserved components of genomes. Although they are routinely used for studying evolutionary histories and assessing new assemblies, current methods do not incorporate information from available genomic data. Here, we first determine the influence of evolutionary history on universal gene content in plants, fungi and animals. We find that across 11,098 genomes comprising 2,606 taxonomic groups, 215 groups significantly vary from their respective lineages in terms of their BUSCO (Benchmarking Universal Single Copy Orthologs) completeness. Additionally, 169 groups display an elevated complement of duplicated orthologs, likely as an artifact of whole genome duplication events. Secondly, we investigate the extent of taxonomic congruence in BUSCO-derived whole-genome phylogenies. For 275 suitable families out of 543 tested, sites evolving at higher rates produce at most 23.84% more taxonomically concordant, and at least 46.15% less terminally variable phylogenies compared to lower-rate sites. We find topological differences between BUSCO concatenated and coalescent trees to be marginal and conclude that higher rate sites from concatenated alignments produce the most congruent and least variable phylogenies. Finally, we show that BUSCO misannotations can lead to misrepresentations of assembly quality. To overcome this issue, we filter a Curated set of BUSCOs (CUSCOs) that provide up to 6.99% fewer false positives compared to the standard BUSCO search and introduce novel methods for comparing assemblies using BUSCO synteny. Overall, we highlight the importance of considering evolutionary histories during assembly evaluations and release the phyca software toolkit that reconstructs consistent phylogenies and reports phylogenetically informed assembly assessments.

genomics↗

bioRxiv2024

A pangenome and pantranscriptome of hexaploid oat

Oat grain is a traditional human food rich in dietary fiber that contributes to improved human health. Interest in the crop has surged in recent years owing to its use as the basis for plant-based milk analogs. Oat is an allohexaploid with a large, repeat-rich genome that was shaped by subgenome exchanges over evolutionary timescales. In contrast to many other cereal species, genomic research in oat is still at an early stage, and surveys of structural genome diversity and gene expression variability are scarce. Here, we present annotated chromosome-scale sequence assemblies of 33 wild and domesticated oats along with an atlas of gene expression across six tissues of different developmental stages in 23 accessions. We describe the interplay of gene expression diversity across subgenomes, accessions and tissues. Gene loss in the hexaploid is accompanied by compensatory up-regulation of the remaining homeologs, but this process is constrained by subgenome divergence. Chromosomal rearrangements have significantly impacted recent oat breeding. A large pericentric inversion associated with early flowering explains distorted segregation on chromosome 7D and a homeologous sequence exchange between chromosomes 2A and 2C in a semidwarf mutant has risen to prominence in Australian elite varieties. The oat pangeome will promote the adoption of genomic approaches to understanding the evolution and adaptation of domesticated oats and will accelerate their improvement.

genomics↗

bioRxiv2024

Chromosome-level haplotype-resolved genome assembly provides insights into the highly heterozygous genome of Italian ryegrass (Lolium multiflorum Lam.)

Italian ryegrass (Lolium multiflorum Lam.) is an important forage grass, providing a major source of feed for ruminants in temperate regions. Due to its highly heterozygous and repeat-rich genome, high-quality chromosome-level genome assemblies are scarce for Italian ryegrass. Here, we sequenced the genome of a genotype from the Italian ryegrass cultivar Rabiosa (hereafter referred to as Rabiosa), and we obtained Oxford Nanopore Technologies long reads ([~]60-fold coverage), Illumina short reads ([~]85-fold coverage) and high-throughput chromosome conformation capture data ([~]60-fold coverage). With Rabiosa as the parent, we constructed an F1 population consisting of 305 individuals, which were genotyped by reduced representation sequencing for linkage map construction and quantitative trait loci (QTL) analysis. Using whole-genome sequencing data of Rabiosa and the genetic linkage map, we first generated a chromosome-level unphased haploid assembly (scaffold N50 of 338.75 Mb, total BUSCO score of 94.60%). Then, based on the unphased assembly and a reference-based phasing approach, we generated a chromosome-level haplotype-resolved assembly containing both haplotypes (scaffold N50 of [~]250 Mb and total BUSCO score of [~]90% for each haplotype). Between the two haplotypes of Rabiosa, we observed a highly collinear gene order at chromosome level and a high sequence variation at local level. With a graph-based reference built from the unphased and the haplotype-resolved assemblies of Rabiosa, we conducted a QTL analysis, and two QTL significantly associated with stem rust resistance were detected. The genome assemblies of Rabiosa will serve as invaluable genomic resources to facilitate genomic applications in forage grass research and breeding.

genomics↗

bioRxiv2024

Oryza genome evolution through a tetraploid lens

Oryza is remarkable genus - with two domesticated (i.e. Asian and African rice) and 25 diploid and tetraploid wild species, 11 extant genome types, and a [~]3.4-fold genome size variation - that possesses a virtually untapped reservoir of genes that can be used for crop improvement. Here we unveil and interrogate 11 new chromosome-level assemblies of nine tetraploid and two diploid wild Oryza species in the context of [~]15 million years of evolution of the genus. We show that the core Oryza (sub)genome across all genome types is only [~]200 Mb and largely syntenic, while the remaining nuclear fractions, spanning [~]80-600 Mb, are intermingled, extremely plastic and rapidly evolving. For the halophyte O. coarctata, we show that - despite the detection of gene fractionation in the subgenomes - homoeologous genes are expressed at higher levels in one subgenome over the other in a mosaic form, thereby showing subgenome equivalence. The integration of these 11 new ultra-high quality reference genomes with our previously published genome data sets provide a nearly complete picture of the consequences of natural and artificial selection across the evolutionary history of Oryza. This in turn opens the door to unlock their genetic potential for future crop improvement and neodomestication.

genomics↗

bioRxiv2023

High-resolution bulked segregant analysis enables candidate gene identification for bacterial wilt resistance in Italian ryegrass

Bacterial wilt, caused by Xanthomonas translucens pv. graminis (Xtg), is a serious disease of economically important forage grasses, including Italian ryegrass (Lolium multiflorum Lam.). A major QTL for resistance to Xtg was previously identified, but the precise location as well as the genetic factors underlying the resistance are yet to be determined. To this end, we applied a bulked segregant analysis (BSA) approach, using whole-genome deep sequencing of pools of the most resistant and most susceptible individuals of a large (n = 7,484) biparental F2 population segregating for resistance to Xtg. Using chromosome-level genome sequences as references, we were able to define a [~]300 kb region highly associated to resistance on pseudo-chromosome 4. Further investigation of this region revealed multiple genes with a known role in disease resistance, including genes encoding for Pik2-like disease resistance proteins, cysteine-rich kinases, and RGA4- and RGA5-like disease resistance proteins. Investigation of allele frequencies in the pools and comparative genome analysis in the grandparents of the F2 population revealed that some of these genes contain variants with allele frequencies that correspond to the expected heterozygosity in the resistant grandparent. This study emphasizes the efficacy combining BSA studies in very large populations with whole genome deep sequencing and high-quality genome sequences to pinpoint regions associated with a binary trait of interest and accurately define a small set of candidate genes. Furthermore, markers identified in this region hold significant potential for marker-assisted breeding strategies to breed resistance to Xtg in Italian ryegrass cultivars more efficiently.

plant biology↗

bioRxiv2023

An improved chromosome-level genome assembly of perennial ryegrass (Lolium perenne L.)

This work is an update and extension of the previously published article "Ultralong Oxford Nanopore Reads Enable the Development of a Reference-Grade Perennial Ryegrass Genome Assembly", by Frei et al.. The published genome assembly of the doubled haploid perennial ryegrass (Lolium perenne L.) genotype Kyuss marked a milestone for forage grass research and breeding. However, order and orientation errors may exist in the pseudo-chromosomes of Kyuss, since barley (Hordeum vulgare L.), which diverged 30 million years ago from perennial ryegrass, was used as the reference to scaffold Kyuss. To correct for structural errors possibly present in the published Kyuss assembly, we de novo assembled the genome again and generated 50-fold coverage high-throughput chromosome conformation capture (Hi-C) data to assist pseudo-chromosome construction. The resulting new chromosome-level assembly showed improved quality with high contiguity (contig N50 = 120 Mb), high completeness (total BUSCO score = 99%), high base-level accuracy (QV = 50) and correct pseudo-chromosome structure (validated by Hi-C contact map). This new assembly will serve as a better reference genome for Lolium spp. and greatly benefit the forage and turf grass research community.

genomics↗

bioRxiv2023

A pooled-sample draft genome assembly provides insights into host plant-specific transcriptional responses of a Solanaceae-specializing pest, Tupiocoris notatus (Hemiptera: Miridae)

The assembly of genomes from pooled samples of genetically heterogenous samples of conspecifics remains challenging. In this study we show that high-quality genome assemblies can be produced from samples of multiple wild-caught individuals. We sequenced DNA extracted from a pooled sample of conspecific herbivorous insects (Hemiptera: Miridae: Tupiocoris notatus) acquired from a greenhouse infestation in Tucson, Arizona (in the range of 30-100 individuals; 0.5 mL tissue by volume) using PacBio highly accurate long reads (HiFi). The initial assembly contained multiple haplotigs (>85% BUSCOs duplicated), but duplicate contigs could be easily purged to reveal a highly complete assembly (95.6% BUSCO, 4.4% duplicated) that is highly contiguous by short-read assembly standards (N50 = 675 kb; Largest contig = 4.3 Mb). We then used our assembly as the basis for a genome-guided differential expression study of host-plant specific transcriptional responses. We found thousands of genes (N = 4982) to be differentially expressed between our new data from individuals feeding on Datura wrightii (Solanaceae) and existing RNA-seq data from Nicotiana attenuata (Solanaceae) fed individuals. We identified many of these genes as previously documented detoxification genes such as glutathione-S-transferases, cytochrome P450s, UDP-glucosyltransferases. Together our results show that long-read sequencing of pooled samples can provide a cost-effective genome assembly option for small insects and provide insights into the genetic mechanisms underlying interactions between plants and herbivorous pests.

genomics↗

bioRxiv2023

An improved genome assembly of the saguaro cactus (Carnegiea gigantea (Engelm.) Britton & Rose).

We present an improved genome assembly of the saguaro cactus (Carnegiea gigantea (Engelm.) Britton & Rose), obtained by incorporating long-read PacBio data to the existing short reads. The assembly improves in terms of total size, contiguity, and accuracy, allowing to extend the range of sequence analyses beyond the single-gene scale. Consequently, the assembly is 16% larger and has 20% more genes, expanding the resources for a neglected yet very remarkable plant family such as Cactaceae. Species taxonomyEukaryota; Viridiplantae; Streptophyta; Streptophytina; Embryophyta; Tracheophyta; Euphyllophyta; Spermatophyta; Magnoliopsida; Mesangiospermae; eudicotyledons; Gunneridae; Pentapetalae; Caryophyllales; Cactineae; Cactaceae; Cactoideae; Echinocereeae; Carnegiea gigantea (Engelm.) Britton & Rose) (also known as saguaro cactus) (NCBI txid: 171969).

genomics↗

bioRxiv2022

Fine-mapping and comparative genomic analysis reveal the gene composition at the S and Z self-incompatibility loci in grasses

Self-incompatibility (SI) is a genetic mechanism of hermaphroditic plants to prevent inbreeding after self-pollination. Allogamous Poaceae species exhibit a unique gametophytic SI system controlled by two multi-allelic and independent loci, S and Z. Despite intense research efforts in the last decades, the genes that determine the initial recognition mechanism are yet to be identified. Here, we report the fine-mapping of the Z-locus in perennial ryegrass (Lolium perenne L.) and provide evidence that the pollen and stigma components are determined by two genes encoding DUF247 domain proteins (ZDUF247-I and ZDUF247-II) and the gene sZ, respectively. The pollen and stigma determinants are located side-by-side and were genetically linked in 10,245 individuals of two independent mapping populations segregating for Z. Moreover, they exhibited high allelic diversity as well as tissue-specific gene expression, matching expected characteristics of SI determinants known from other systems. Revisiting the S-locus using the latest high-quality whole-genome assemblies revealed a similar gene composition and structure as found for Z, supporting the hypothesis of a duplicated origin of the two-locus SI system of grasses. Ultimately, comparative genomic analyses across a wide range of self-compatible and self-incompatible Poaceae species revealed that the absence of a functional copy of at least one of the six putative SI determinants is accompanied by a self-compatible phenotype. Our study provides new insights into the origin and evolution of the unique gametophytic SI system in one of the largest and economically most important plant families.

plant biology↗

bioRxiv2022

Pan-genome inversion index reveals evolutionary insights into the subpopulation structure of Asian rice (Oryza sativa)

Understanding and exploiting genetic diversity is a key factor for the productive and stable production of rice. Utilizing 16 high-quality genomes that represent the subpopulation structure of Asian rice (O. sativa), plus the genomes of two close relatives (O. rufipogon and O. punctata), we built a pan-genome inversion index of 1,054 non-redundant inversions that span an average of [~] 14% of the O. sativa cv. Nipponbare reference genome sequence. Using this index we estimated an inversion rate of 1,100 inversions per million years in Asian rice, which is 37 to 73 times higher than previously estimated for plants. Detailed analyses of these inversions showed evidence of their effects on gene regulation, recombination rate, linkage disequilibrium and agronomic trait performance. Our study uncovers the prevalence and scale of large inversions ([≥] 100 kb) across the pan-genome of Asian rice, and hints at their largely unexplored role in functional biology and crop performance.

genomics↗

bioRxiv2021

Evidence for high intergenic sequence variation in heterozygous Italian ryegrass (Lolium multiflorum Lam.) genome revealed by a high-quality draft diploid genome assembly

BackgroundOver the last decade, progress in DNA sequencing technologies and assembly methods allowed plant scientists to move beyond the use of model organisms and work directly on the genomes of the major crops. Forage grass research can also benefit from this revolution, enabling progress in population genetic studies, functional biology, and genomics-assisted breeding. Due to its large genome size and high repeat content, so far only incomplete and fragmented assemblies are available for the grasses of the Lolium and Festuca species complex. FindingsHere, we report a highly contiguous draft assembly of Italian ryegrass (L. multiflorum Lam.), spanning 4.5 Gb and with a N50 of 3 Mb, containing ~70,000 gene models. Thanks to its relatedness to barley, 78% of the assembly was anchored on seven pseudomolecules. The high heterozygosity of the plant allowed obtaining a diploid assembly - i.e. across 95% of the assembly, both alleles were assembled on separate sequences. This feature allowed unraveling a very high amount of intergenic sequence variation between allelic sequences. ConclusionsWe present a nearly complete genome assembly of a genotype used in contemporary Swiss forage grass breeding programs. This work shows how genomic research has improved, allowing to decode the genetic code of large, complex, and heterozygous plants. It also allows the functional characterization of the ryegrass gene repertoire and the large-scale development of molecular markers. Furthermore, it paves the road for a reference-based characterization and exploitation of the genetic variation within the Lolium and Festuca species complex.

genomics↗

bioRxiv2021

Identification of candidate genes for self-compatibility in perennial ryegrass (Lolium perenne L.)

Self-incompatibility (SI) is a genetic mechanism preventing self-pollination in approximately 40% of plant species. Two multiallelic loci, called S and Z, control the gametophytic SI system of the grass family (Poaceae), which contains all major forage grasses. Loci independent from S and Z have been reported to disrupt SI and lead to self-compatibility (SC). A locus causing SC in perennial ryegrass (Lolium perenne L.) was previously mapped on linkage group (LG) 5 in a F2 population segregating for SC. Using a subset of the same population (n=68), we first performed low-resolution quantitative trait locus (QTL) mapping to exclude the presence of additional, previously undetected contributors to SC. The previously reported QTL on LG 5 explained 38.4% of the phenotypic variation, and no significant contribution from other genomic regions was found. This was verified by the presence of significantly distorted markers in the region overlapping with the QTL. Second, we fine mapped the QTL to 0.26 cM using additional 2,056 plants and 23 novel sequence-based markers. Using an Italian ryegrass (Lolium multiflorum Lam.) genome assembly as reference, the markers flanking SC were estimated to span a ~3 Mb region encoding for 57 predicted genes. Among these, seven genes were proposed as relevant candidate genes based on their annotation and function described in previous studies. Our work is a step forward to identify SC genes in forage grasses and provides diagnostic markers for marker-assisted introgression of SC into elite germplasm. Key messageA previously reported QTL conferring self-compatibility to perennial ryegrass was fine mapped to a 0.26 cM locus, corresponding to an estimated ~ 3 Mb physical region containing 57 predicted protein-encoding genes.

plant biology↗

bioRxiv2020

A new (old) approach to genotype-based phylogenomic inference within species, with an example from the saguaro cactus (Carnegiea gigantea)

AO_SCPLOWBSTRACTC_SCPLOWGenome sequence data are routinely being used to infer phylogenetic history within and between closely related diploid species, but few tree inference methods are specifically tailored to diploid genotype data. Here we re-examine the method of "polymorphism parsimony" (Inger 1967; Farris 1978; Felsenstein 1979), originally introduced to study morphological characters and chromosome inversion polymorphisms, to evaluate its utility for unphased diploid genotype data in large scale phylogenomic data sets. We show that it is equivalent to inferring species trees by minimizing deep coalescences--assuming an infinite sites model. Two potential advantages of this approach are scalability and estimation of a rooted tree. As with some other single nucleotide polymorphism (SNP) based methods, it requires thinning of data sets to statistically independent sites, and we describe a genotype-based test for phylogenetic independence. To evaluate this approach in genome scale data, we construct intraspecific phylogenies for 10 populations of the saguaro cactus using 200 Gbp of resequencing data, and then use these methods to test whether the population with highest genetic diversity corresponds to the root of the genotype trees. Results were highly congruent with the (unrooted) trees obtained using SVDquartets, a scalable alternative method of phylogenomic inference.

evolutionary biology↗

bioRxiv2020

Chromosome-scale de novo diploid assembly of the apple cultivar 'Gala Galaxy'

Apple (Malus x domestica) is one of the most important fruit crops in terms of worldwide production. Due to its self-incompatibility system and the long juvenile period, breeding of new apple cultivars combining traits desired by growers (e.g. yield, pest and disease resistance) and consumers (e.g. fruit size, color, and flavor) is a long and complex process. Genomics-assisted breeding strategies can facilitate the selection of germplasm leading to new cultivars. While the most complete apple genome assemblies available to date are from anther-derived homozygous lines, de novo assembly of apple genomes encompassing the natural heterozygosity remains challenging. Using long- and short-read sequencing technologies in combination with optical mapping, we de novo assembled a diploid and heterozygous genome of the apple cultivar Gala Galaxy. This approach resulted in 154 hybrid scaffolds (N50 = 34.3 Mb) spanning 999.9 Mb and in 414.7 Mb of unscaffolded sequences. Anchoring 31 scaffolds with a genetic map was sufficient to represent an entire haploid genome of 17 pseudomolecules (719.4 Mb). The remaining sequences were assembled in a second set of 17 pseudomolecules, which spanned 601 Mb, leaving 80.6 Mb of unplaced sequences. A total of 41,264 genes were annotated using 74,900 transcripts derived from RNA sequencing of pooled leaf tissue samples. This study provides a high-quality diploid reference genome sequence encompassing the natural heterozygosity of the widely popular cultivar Gala Galaxy. The DNA sequence resources and the assembly described here will serve as a solid foundation for fundamental and applied apple breeding research.

genomics↗

bioRxiv2019

A chromosome-scale assembly of allotetraploid Brassica juncea (AABB) elucidates comparative architecture of the A and B genomes

Brassica juncea (AABB; genome size [~]920 Mb), commonly referred to as mustard, is a natural allopolyploid of two diploid species - B. rapa (AA) and B. nigra (BB). We report a highly contiguous genome assembly of an oleiferous type of B. juncea variety Varuna, an archetypical Indian gene pool line of mustard, with [~]100x PacBio single-molecule real-time (SMRT) reads providing contigs with an N50 value of >5Mb. Assembled contigs were corrected and scaffolded with BioNano optical mapping. Three different linkage maps containing a large number of GBS markers were developed and used to anchor scaffolds/contigs to the 18 linkage groups of B. juncea. The resulting chromosome-scale assembly is a significant improvement over the previous draft assembly of B. juncea Tumida, a vegetable type of mustard. The assembled genome was characterized for transposons, centromeric repeats, gene content, and gene block associations. Both A and B genomes contain highly fragmented gene block arrangements. In comparison to the A genome, the B genome contains a significantly higher content of LTR/Gypsy retrotransposons, distinct centromeric repeats and a large number of B. nigra specific gene clusters that break the gene collinearity between the A and the B genomes. The genome assembly reported here will provide a fillip to the breeding work on oleiferous types of mustard that are grown extensively in the dry land areas of South Asia and elsewhere.

genomics↗