Editorial: Genome wide association studies and genomic selection for crop improvement in the era of Big Data

The exploitation of the genetic diversity of crops is essential for breeding purposes, as the identification of useful/beneficial alleles for target traits within plant genetic resources allows the development of new varieties capable of responding to the challenges of global agriculture (Food and Agriculture Organization of the United Nations, 2010). Whole genome re-sequencing, genome skimming, fractional genome sequencing strategies, and high-density genotyping arrays enable large-scale assessment of genetic diversity for a wide range of species, including major and “orphan” crops (D’Agostino and Tripodi, 2017; Rasheed et al., 2017). This is however of limited value unless associated with adaptation and functional improvement of crops. Recently, several advances in high-throughput phenotyping have overcome the “phenotyping bottleneck” (Walter et al., 2015; Pieruschka and Schurr, 2019; Song et al., 2021), making available robust phenotypic data points acquired following the precise characterization of the agronomic and physiological attributes of crops. More and more studies are taking advantage of these scientific advances and of data science techniques to uncover the genome-to-phenome relationship and unlock the breeding potential of plant genetic resources. Genome-wide association studies (GWAS) and genomic selection (GS) are powerful data science approaches to investigate marker-trait associations (MTAs) for the basic understanding of simple and complex adaptive and functional traits (Liu and Yan, 2019; Voss-Fels et al., 2019; Varshney et al., 2021). Both approaches accelerate the rate of genetic gain in crops and reduce the breeding cycle in a cost-effective manner. For this Research Topic we sought high-quality contributions, covering various aspects of genomics-assisted-breeding: increase in yield, improvement of nutritional content and end-use quality of crops, climate-smart agriculture, cropping systems in agriculture. We did not miss to ask for contributions on technical challenges related to the design of GWAS and GS experiments and data analysis

The Algorithm Theoretical Basis Document for Tidal Corrections

This Algorithm Theoretical Basis Document deals with the tidal corrections that need to be applied to range measurements made by the Geoscience Laser Altimeter System (GLAS). These corrections result from the action of ocean tides and Earth tides which lead to deviations from an equilibrium surface. Since the effect of tides is dependent of the time of measurement, it is necessary to remove the instantaneous tide components when processing altimeter data, so that all measurements are made to the equilibrium surface. The three main tide components to consider are the ocean tide, the solid-earth tide and the ocean loading tide. There are also long period ocean tides and the pole tide. The approximate magnitudes of these components are illustrated in Table 1, together with estimates of their uncertainties (i.e. the residual error after correction). All of these components are important for GLAS measurements over the ice sheets since centimeter-level accuracy for surface elevation change detection is required. The effect of each tidal component is to be removed by approximating their magnitude using tidal prediction models. Conversely, assimilation of GLAS measurements into tidal models will help to improve them, especially at high latitudes

Rotation Periods of Open Cluster Stars, II

We present the results from a photometric monitoring program of 21 stars observed during 1992 in the Pleiades and Alpha Persei open clusters. Period determinations for 16 stars are given, 13 of which are the first periods reported for these stars. Brightness variations for an additional five cluster stars are also given. One K dwarf member of the a Per cluster is observed to have a period of rotation of only 4.39 hr, perhaps the shortest period currently known among BY Draconis variables. The individual photometric measurements have been deposited with the NSSDC. Combining current X-ray flux determinations with known photometric periods, we illustrate the X-ray activity/rotation relation among Pleiades K dwarfs based on available data

HTLV-1 clonality during chronic infection and BLV clonality during primary infection

peer reviewedaudience: researcherHTLV-1 clonality during chronic infection and BLV clonality during primary infection Nicolas A Gillet1,2*, Carol Hlela1, Tine Verdonck3, Eduardo Gotuzzo3, Daniel Clark3, Sabrina Rodriguez2, Nirav Malani4, Anat Melamed1, Niall Gormley5, Richard Carter5, David Bentley5, Charles Berry6, Frederic D Bushman4, Graham P Taylor7, Luc Willems2, Charles R M Bangham1 1Department of Immunology, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. 2Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) of University of Liège (ULg), Liège, 4000, Belgium. 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 4Department of Microbiology, University of Pennsylvania School of Medicine, Pennsylvania, Philadelphia, PA, 19104, USA. 5Illumina, Chesterford Research Park, Essex, Little Chesterford, CB10 1XL, UK. 6University of California, California, La Jolla San Diego, CA, 92093-0901, USA. 7Department of Genitourinary Medicine and Communicable Diseases, Wright-Fleming Institute, Imperial College London, London, W2 1PG, UK. HTLV-1 persists by driving clonal proliferation of infected T-lymphocytes. A high proviral load predisposes to the inflammatory and malignant diseases associated with HTLV-1. Yet the reasons for the remarkable variation within and between individuals in the abundance of HTLV-1-infected clones remain unknown. We demonstrate that negative selection dominates during chronic infection, favouring establishment of proviruses integrated in transcriptionally silenced DNA: this selection is significantly stronger in asymptomatic carriers. We postulated that this selection occurred mainly during the primary infection. We are testing this hypothesis in an animal model by studying the BLV clonality during the primary infection in cows. By measuring the proviral load, the anti-BLV immune response and the BLV clonality we aim to quantify the impact of the immune response on the rate of infectious spread and on the selection of proviruses inserted in a particular genomic environment. Co-infection with Strongyloides stercoralis or Staphylococcus appears to be another risk factor for the development of HTLV-1 associated diseases. We observed that HTLV-1 clonality is altered by co-infection with these pathogens with an increase of both the number and the abundance of the infected T-cell clones. The genomic characteristics of the proviral integration sites in the most abundant clones differ significantly between co-infected individuals and those with HTLV-1 alone, implying the existence of different selection forces in co-infected patients. The rate of appearance of new clones in patients co-infected with Strongyloides stercoralis is higher than in patients with HTLV-1 alone. By comparing skin lesions and blood samples from patients with Infective Dermatitis associated with HTLV-1 (IDH), we observed a significant proportion of distinct infected clones between the two compartments. The skin lesions seem to be a site for HTLV-1 infectious spread

The Algorithm Theoretical Basis Document for the Derivation of Range and Range Distributions from Laser Pulse Waveform Analysis for Surface Elevations, Roughness, Slope, and Vegetation Heights

The primary purpose of the GLAS instrument is to detect ice elevation changes over time which are used to derive changes in ice volume. Other objectives include measuring sea ice freeboard, ocean and land surface elevation, surface roughness, and canopy heights over land. This Algorithm Theoretical Basis Document (ATBD) describes the theory and implementation behind the algorithms used to produce the level 1B products for waveform parameters and global elevation and the level 2 products that are specific to ice sheet, sea ice, land, and ocean elevations respectively. These output products, are defined in detail along with the associated quality, and the constraints, and assumptions used to derive them

Thiamin and Riboflavin in Human Milk: Effects of Lipid-Based Nutrient Supplementation and Stage of Lactation on Vitamer Secretion and Contributions to Total Vitamin Content

While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin-monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid-based nutrient supplements (LNS) or a control group, to investigate each vitamer’s contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography-fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra-performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin-pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9–4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151μg/L (TMP), 13.3 versus 10.5μg/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8–19.6μg/L (LNS) versus 5.0–7.4μg/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92–94:6–8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the mammary gland

An Approach to Identify Gene-Environment interactions and Reveal New Biological insight in Complex Traits

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. to address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci (6 independent signals) interacted with either cigarette smoking or alcohol consumption for serum lipids, and empirically demonstrate that interaction and mediation are the major contributors to genetic effect size heterogeneity across populations. The estimated lower bound of the interaction and environmentally mediated heritability is significant (P \u3c 0.02) for low-density lipoprotein cholesterol and triglycerides in Cross-Population data. Our study improves the understanding of the genetic architecture and environmental contributions to complex traits

Treg depletion potentiates checkpoint inhibition in claudin-low breast cancer

Claudin-low breast cancer is an aggressive subtype that confers poor prognosis and is found largely within the clinical triple-negative group of breast cancer patients. Here, we have shown that intrinsic and immune cell gene signatures distinguish the claudin-low subtype clinically as well as in mouse models of other breast cancer subtypes. Despite adaptive immune cell infiltration in claudin-low tumors, treatment with immune checkpoint inhibitory antibodies against cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and programmed death receptor 1 (PD-1) were ineffective in controlling tumor growth. CD4+FoxP3+ Tregs represented a large proportion of the tumor-infiltrating lymphocytes (TILs) in claudin-low tumors, and Tregs isolated from tumor-bearing mice were able to suppress effector T cell responses. Tregs in the tumor microenvironment highly expressed PD-1 and were recruited partly through tumor generation of the chemokine CXCL12. Antitumor efficacy required stringent Treg depletion combined with checkpoint inhibition; delays in tumor growth were not observed using therapies that modestly diminished the number of Tregs in the tumor microenvironment. This study provides evidence that the recruitment of Tregs to the tumor microenvironment inhibits an effective antitumor immune response and highlights early Treg recruitment as a possible mechanism for the lack of response to immune checkpoint blockade antibodies in specific subtypes of cancer that are heavily infiltrated with adaptive immune cells

Sowing the wheat seeds of Afghanistan's future

Societal Impact Statement: The production and availability of food underpins societal stability. In Afghanistan, wheat is the major arable agricultural crop and source of dietary energy. The withdrawal of NATO allies and partner countries from Afghanistan presents numerous well‐documented societal and political challenges and has impacts on immediate and longer‐term food security. Conflict‐impacted irrigation infrastructure coupled with growing climate instability have also contributed markedly to reductions in current food, and specifically wheat, production. Here, we review the status of Afghan wheat improvement and propose a research agenda to support the regeneration of Afghanistan's wheat and agricultural sector. Summary: Afghanistan is a country with diverse natural ecologies in a largely arid and mountainous region. The rural sector is still considered to drive economic potential. Current social, political and economic instability along with climatic challenges are driving food and water insecurity in the wider region. In the short term, it is likely that this and the associated challenges of displacement and unemployment can only be addressed by humanitarian intervention and agrifood and nutrition support. In the medium to long term, drought, and heat, probably linked to climate change, will pose recurrent challenges for agriculture and food security that will require a much broader set of interventions to secure the rural population's livelihoods. The genetic gap, among other major challenges, must be addressed if Afghanistan is to develop its agricultural potential leading to income and livelihood improvements for farmers and stable and accessible supplies for consumers. Only thereby will the country be enabled to reap the important and long‐sought trade and food security benefits derived from self‐sufficiency. Here, we highlight the agricultural challenges facing Afghanistan and propose forward strategies for ensuring the future stability of wheat production, the cornerstone of Afghan agriculture