Novel Sequencing and Genomic Technologies Revolutionized Rice Genomic Study and Breeding

Rice is one of the most important food crops worldwide. Population growth and climate change posed great challenges for further rice production. In the past decade, we have witnessed an explosive development in novel sequencing and genomic technologies. These technologies have been widely applied in rice genomic study and improvement processes, and contributed greatly to increase the efficiency and accuracy of rice breeding. On the other hand, novel sequencing and genomic technologies also promote the shift of breeding schemes from conventional field selection processes to genomic assisted breeding. These technologies have revolutionized almost every aspect of rice study and breeding. Here, we systematically sorted out and reviewed the progress and advancements of sequencing and genomic technologies. We further discussed how these technologies were incorporated into rice breeding practices and helped accelerate the rice improvement process. Finally, we reflected on how to further utilize novel sequencing and genomic technologies in rice genetic improvement, as well as the future trends of advancement for these technologies. It can be expected that, as the sequencing and genomic technologies will develop much more quickly in the future, and be combined with novel bioinformatics tools, rice breeding will move forward into the genomic assisted era.

Alignment of spatial genomics and histology data using deep Gaussian processes

Spatially-resolved genomic technologies have allowed us to study the physical organization of cells and tissues, and promise an understanding of the local interactions between cells. However, it remains difficult to precisely align spatial observations across slices, samples, scales, individuals, and technologies. Here, we propose a probabilistic model that aligns a set of spatially-resolved genomics and histology slices onto a known or unknown common coordinate system into which the samples are aligned both spatially and in terms of the phenotypic readouts (e.g., gene or protein expression levels, cell density, open chromatin regions). Our method consists of a two-layer Gaussian process: the first layer maps the observed samples' spatial locations into a common coordinate system, and the second layer maps from the common coordinate system to the observed readouts. Our approach also allows for slices to be mapped to a known template coordinate space if one exists. We show that our registration approach enables complex downstream spatially-aware analyses of spatial genomics data at multiple resolutions that are impossible or inaccurate with unaligned data, including an analysis of variance, differential expression across the z-axis, and association tests across multiple data modalities.

Integrated Genomic and Bioinformatics Approaches to Identify Molecular Links between Endocrine Disruptors and Adverse Outcomes

Exposure to Endocrine Disrupting Chemicals (EDC) has been linked with several adverse outcomes. In this review, we examine EDCs that are pervasive in the environment and are of concern in the context of human, animal, and environmental health. We explore the consequences of EDC exposure on aquatic life, terrestrial animals, and humans. We focus on the exploitation of genomics technologies and in particular whole transcriptome sequencing. Genome-wide analyses using RNAseq provides snap shots of cellular, tissue and whole organism transcriptomes under normal physiological and EDC perturbed conditions. A global view of gene expression provides highly valuable information as it uncovers gene families or more specifically, pathways that are affected by EDC exposures, but also reveals those that are unaffected. Hypotheses about genes with unknown functions can also be formed by comparison of their expression levels with genes of known function. Risk assessment strategies leveraging genomic technologies and the development of toxicology databases are explored. Finally, we review how the Adverse Outcome Pathway (AOP) has exploited this high throughput data to provide a framework for toxicology studies.

Sustainable animal genetic improvement

Well designed and targeted animal breeding programs allow a sustainable genetic improvement of livestock with increases in animal productivity of 1-2% per annum. Over time, massive improvements have been achieved, e.g. in dairy and pig and poultry production systems, now resulting in higher production that requires much fewer input of resources. Although reproductive and genomic technologies contribute nowadays to increases in rates of genetic improvement, the key to successful breeding programs lies in a strong focus on simple and well-defined breeding objectives, effective investment in trait measurement, a clear understanding of the structure of the breeding program, and efficient systems for genetic evaluation, selection and mating of elite animals. The dissemination of the genetics of selected animals to the wider population also needs consideration, requiring commercial farmers or smallholders to have the means to have access to improved genetics as well as an understanding of the value of using improved bulls. Definition of the breeding objectives as well as evaluation of genetic merit needs to be based on the local environment. Compared with other interventions to improve productivity and stability, genetic improvement is a critical and cost-effective approach as genetic gains are permanent and cumulative.

Advancing genomic technologies and clinical awareness accelerates discovery of disease-associated tandem repeat sequences

Expansions of gene-specific DNA tandem repeats (TRs), first described in 1991 as a disease-causing mutation in humans, are now known to cause >60 phenotypes, not just disease, and not only in humans. TRs are a common form of genetic variation with biological consequences, observed, so far, in humans, dogs, plants, oysters, and yeast. Repeat diseases show atypical clinical features, genetic anticipation, and multiple and partially penetrant phenotypes among family members. Discovery of disease-causing repeat expansion loci accelerated through technological advances in DNA sequencing and computational analyses. Between 2019 and 2021, 17 new disease-causing TR expansions were reported, totaling 63 TR loci (>69 diseases), with a likelihood of more discoveries, and in more organisms. Recent and historical lessons reveal that properly assessed clinical presentations, coupled with genetic and biological awareness, can guide discovery of disease-causing unstable TRs. We highlight critical but underrecognized aspects of TR mutations. Repeat motifs may not be present in current reference genomes but will be in forthcoming gapless long-read references. Repeat motif size can be a single nucleotide to kilobases/unit. At a given locus, repeat motif sequence purity can vary with consequence. Pathogenic repeats can be “insertions” within nonpathogenic TRs. Expansions, contractions, and somatic length variations of TRs can have clinical/biological consequences. TR instabilities occur in humans and other organisms. TRs can be epigenetically modified and/or chromosomal fragile sites. We discuss the expanding field of disease-associated TR instabilities, highlighting prospects, clinical and genetic clues, tools, and challenges for further discoveries of disease-causing TR instabilities and understanding their biological and pathological impacts—a vista that is about to expand.

Haplotype-resolved inversion landscape reveals hotspots of mutational recurrence associated with genomic disorders

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1-retrotransposition; 80% of the larger inversions are balanced and affect twice as many base pairs as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or mobile elements. Since this suggests recurrence due to non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7*10-4 per locus and generation. Recurrent inversions exhibit a sex-chromosomal bias, and significantly co-localize to the critical regions of genomic disorders. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes to disease-causing CNVs.

Biotech value chain and technologies for COVID-19 research areas for collaboration on cost quality tradeoff with tool companies

BACKGROUND: Technologies for COVID-19 are in high demand, and supply chains from biotech and pharma industries face critical supply issues. OBJECTIVE: This paper discusses the case on mRNA technologies and quality assurance issues. METHODS: Interviews with managers of biotech companies were performed. These helped to prepare biotech panels at a roundtable on quality of medicine, organized by the Polish Academy of Sciences in Paris (PAN) in 2021. RESULTS: This paper analyzes the new mRNA technology and shows the importance of emerging new biotech firms, especially tool companies providing services in quality assurance. It highlights research areas and types of survey instruments with academic collaborators, to better understand the economics of mRNA technology platforms. CONCLUSIONS: A future research agenda for collaboration with academic communities is proposed on cost-quality trade-offs and clinical quality attributes for such genomic technologies.

Envisaging an Effective Global Long-Term Agrobiodiversity Conservation System That Promotes and Facilitates Use

Genebanks were established out of a recognised need not just to provide genetic variation to support breeding objectives but to prevent crop diversity from being lost entirely for future users. Such conservation objectives may have led, over the past few decades, to a gradually diminishing connection between genebanks and current users of diversity. While there continues to be large-scale distribution of germplasm from genebanks to recipients worldwide, relatively little is known or published about the detailed trends in the demand for genebank materials. Meanwhile, the rapid expansion of the applications and uses of modern genomic technologies and approaches is, undoubtedly, having a transformational impact on breeding, research and the demand for certain genetic resources and associated data. These trends will require genebanks to be responsive and to adapt. They also provide important opportunities for genebanks to reorganize and become more efficient individually and as a community. Ultimately, future challenges and opportunities are likely to drive more demand for genetic diversity and provide an important basis for genebanks to gear up.

Public Perceptions Regarding Genomic Technologies Applied to Breeding Farm Animals: A Qualitative Study

The societal acceptability of different applications of genomic technologies to animal production systems will determine whether their innovation trajectories will reach the commercialisation stage. Importantly, technological implementation and commercialisation trajectories, regulation, and policy development need to take account of public priorities and attitudes. More effective co-production practices will ensure the application of genomic technologies to animals aligns with public priorities and are acceptable to society. Consumer rejection of, and limited demand for, animal products developed using novel genomic technologies will determine whether they are integration into the food system. However, little is known about whether genomic technologies that accelerate breeding but do not introduce cross-species genetic changes are more acceptable to consumers than those that do. Five focus groups, held in the north east of England, were used to explore the perceptions of, and attitudes towards, the use of genomic technologies in breeding farm animals for the human food supply chain. Overall, study participants were more positive towards genomic technologies applied to promote animal welfare (e.g., improved disease resistance), environmental sustainability, and human health. Animal “disenhancement” was viewed negatively and increased food production alone was not perceived as a potential benefit. In comparison to gene editing, research participants were most negative about genetic modification and the application of gene drives, independent of the benefits delivered.