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At least 109 records · Page 6
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Unraveling plant phenotype to genotype associations with daily hyperspectral traits in Populus trichocarpa

Hyperspectral remote sensing is a powerful, high-throughput phenotyping tool that quantifies physiologically and structurally relevant wavelengths across diverse genotypes and over varying temporal scales. In this study, we combined tower-based continuous hyperspectral sensing with genome-wide association studies to analyze 1423 wavebands (400-900 nm) and derivative vegetation indices across 505 genotypes and the genetic architecture of hyperspectral phenotypes over time in Populus trichocarpa Torr. & Gray grown under field conditions. Wavelengths related to chlorophyll and carotenoid absorption spectra exhibited the strongest genetic variation resulting in 98 significant SNP associations. Notably, we found substantial overlap in genetic association between the blue and red spectral regions, indicative of carotenoids and chlorophyll, respectively, and identified more than 10 candidate genes associated with chloroplast function, underpinning photosynthetic activity. Furthermore, fluctuations in associations for vegetative indices, such as the chlorophyll:carotenoid index (CCI), across the growing season reveal a temporally dynamic genetic architecture of physiological traits associated with fall senescence of this temperate tree species. Finally, we also observed correlations (spearman rho = 0.3, p < 1x10 −8 ) between individual wavebands or vegetative indices and growth rate, assessed as the relative change of tree height over the growing season. The growth rate prediction was substantially improved by a regularization multivariate model (spearman rho>0.5, p < 1x10 −16 ), reinforcing the value of hyperspectral measurements for predicting traits linked to tree productivity. These findings highlight the potential of high-throughput, rapid, hyperspectral genome wide association studies GWAS to uncover physiologically meaningful genetic variation and offer promising insights for future acceleration for plant breeding.

09 BIOMASS FUELS↗
DOE OSTI2016

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR)

Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients. Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0–3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P = 0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P = 0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events. Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations. - Highlights: • NQO1 C609T variant is associated with warfarin induced bleeding at therapeutic INR. • Haplotypes of CYP2C9 (1*2 or 1*3) are also associated with bleeding events. • VKORC1, Factor VII, and EPHX1 genotypes were not associated with bleeding risk.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

In silico pharmacogenetic approach: The natalizumab case study

Natalizumab is a humanized monoclonal antibody to α{sub 4}β{sub 1} integrin and is approved for the treatment of Multiple Sclerosis. In patients there is a great variation in drug response and there is much evidence that genetic contributors play an important role in defining an individual's susceptibility. Natalizumab binds to α{sub 4}-residues Gln-152, Lys-201, Lys256, and these seem to be essential for its activity. Studies on a range of species in disease model have showed a loss of reactivity when any one of those three residues were different to human. Based on these animal studies, we thought that the single nucleotide polymorphism in the ITGA4 human gene causing a lysine to arginine transversion at amino acid position 256 require further investigations in the context of individual drug susceptibility. So, the aim of our study was to investigate the association between this genetic polymorphism and the resistance to natalizumab. We had applied molecular dynamics simulation to study the possible conformational changes induced by Lys256Arg transversion on the overall structure of integrin and we have analyzed the binding affinities of natalizumab in the non-mutated and mutated structures through HINT score. We found that this SNP does not affect the VLA4-natalizumab interaction. Instead, the binding affinities are slightly higher in the mutated complex than in the wild-type. We reported one of the first work in which MD simulation was applied in the pharmacogenetic context, and this approach is rapid and cost effective, since a population survey is carried out only after the positive prediction of simulation. - Highlights: • Untraditional computational approach to discover drugs mechanisms of action (MOA) in pharmacogenetic • Molecular dynamics to predict protein-monoclonal antibody complexes for multiple sclerosis • Computational prediction of mutation behavior to determine or not a human population survey.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Inhalation exposure to three-dimensional printer emissions stimulates acute hypertension and microvascular dysfunction

Fused deposition modeling (FDM™), or three-dimensional (3D) printing has become routine in industrial, occupational and domestic environments. We have recently reported that 3D printing emissions (3DPE) are complex mixtures, with a large ultrafine particulate matter component. Additionally, we and others have reported that inhalation of xenobiotic particles in this size range is associated with an array of cardiovascular dysfunctions. Sprague-Dawley rats were exposed to 3DPE aerosols via nose-only exposure for ~ 3 h. Twenty-four hours later, intravital microscopy was performed to assess microvascular function in the spinotrapezius muscle. Endothelium-dependent and -independent arteriolar dilation were stimulated by local microiontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). At the time of experiments, animals exposed to 3DPE inhalation presented with a mean arterial pressure of 125 ± 4 mm Hg, and this was significantly higher than that for the sham-control group (94 ± 3 mm Hg). Consistent with this pressor response in the 3DPE group, was an elevation of ~ 12% in resting arteriolar tone. Endothelium-dependent arteriolar dilation was significantly impaired after 3DPE inhalation across all iontophoretic ejection currents (0–27 ± 15%, compared to sham-control: 15–120 ± 21%). Endothelium-independent dilation was not affected by 3DPE inhalation. These alterations in peripheral microvascular resistance and reactivity are consistent with elevations in arterial pressure that follow 3DPE inhalation. Future studies must identify the specific toxicants generated by FDM™ that drive this acute pressor response.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗
DOE OSTI2018

DA-Raf, a dominant-negative antagonist of the Ras–ERK pathway, is a putative tumor suppressor

Highlights: • DA-Raf binds to oncogenic Ras and consequently suppresses the ERK pathway. • DA-Raf suppresses oncogenic Ras-induced transformation and tumorigenesis. • DA-Raf mutants cannot bind to oncogenic Ras or suppress the ERK pathway. • DA-Raf mutants cannot suppress oncogenic Ras-induced transformation and tumorigenesis. • DA-Raf is a tumor suppressor protein against Ras-induced tumorigenesis. Activating mutations of RAS genes, particularly KRAS, are detected with high frequency in human tumors. Mutated Ras proteins constitutively activate the ERK pathway (Raf–MEK–ERK phosphorylation cascade), leading to cellular transformation and tumorigenesis. DA-Raf1 (DA-Raf) is a splicing variant of A-Raf and contains the Ras-binding domain (RBD) but lacks the kinase domain. Accordingly, DA-Raf antagonizes the Ras–ERK pathway in a dominant-negative fashion and suppresses constitutively activated K-Ras-induced cellular transformation. Thus, we have addressed whether DA-Raf serves as a tumor suppressor of Ras-induced tumorigenesis. DA-Raf(R52Q), which is generated from a single nucleotide polymorphism (SNP) in the RBD, and DA-Raf(R52W), a mutant detected in a lung cancer, neither bound to active K-Ras nor interfered with the activation of the ERK pathway. They were incapable of suppressing activated K-Ras-induced cellular transformation and tumorigenesis in mice, in which K-Ras-transformed cells were transplanted. Furthermore, although DA-Raf was highly expressed in lung alveolar epithelial type 2 (AE2) cells, its expression was silenced in AE2-derived lung adenocarcinoma cell lines with oncogenic KRAS mutations. These results suggest that DA-Raf represents a tumor suppressor protein against Ras-induced tumorigenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Dye Encapsulation in Fluorescent Core–Shell Silica Nanoparticles as Probed by Fluorescence Correlation Spectroscopy

Synthetic advances in the formation of ultrasmall (<10 nm) fluorescent poly(ethylene glycol)-coated (PEGylated) core–shell silica nanoparticles (SNPs), enabling improved particle size and surface chemical property control, have led to successful clinical translation of SNPs as diagnostic probes in oncology. Despite the success of such probes, details of the dye incorporation and resulting silica architecture are still poorly understood. Here, we employ afterpulse-corrected fluorescence correlation spectroscopy (FCS) to monitor fast fluorescence fluctuations (lag times <10 –5 s) of the negatively charged cyanine dye Cy5 as a probe to study such details for dye encapsulation in 5 nm silica cores of PEGylated core–shell SNPs (C dots). Upon deposition of additional silica shells over the silica core, we find that the amplitude of photoinduced cis–trans isomerization decreases, suggesting that the Cy5 dyes are located near or on the surface of the original SNP cores. In combination with time-correlated fluorescence decay measurements, we deduce radiative and nonradiative rates of the Cy5 dye in these particles. Finally, results demonstrate that FCS is a well-suited tool to investigate aspects of the photophysics of fluorescent nanoparticles, and that conformational changes of cyanine dyes like Cy5 are excellent indicators for the local dye environment within ultrasmall SNPs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

A Multiplexed Quantitative Analysis of Germline Single Amino Acid Variants by Targeted Proteomics in Nondepleted Human Plasma

Single amino acid variants (SAAVs) in protein sequences are often a direct result of single-nucleotide polymorphisms (SNPs). Certain germline SAAVs have shown biological relevance in different disease conditions but lack precise quantification in circulation, which could hinder functional investigations and progress in biomarker development. Here, we have developed a multiplexed liquid chromatography-selected reaction monitoring (LC-SRM) assay that monitors 5 wild-type and variant peptide pairs (Complement Factor B: CFB-R32Q/R32W, Clusterin: CLU-N317H, Fetuin B: FETUB-K360R, and Kininogen: KNG1-L212P) in nondepleted human plasma. The assay was optimized for imprecision, linearity, stability, and calibration assessments with CVs of under 20%. The wild-type and variant peptide pairs were characterized in a set of healthy individual plasma samples. These target identifications were also validated by SNP genotyping with more than 99% accuracy. For all protein targets, we observed significantly lower concentrations of WT species in the presence variant peptides. In CFB, the concentration of R32Q was significantly lower than its counterpart R32W variant and WT species. Furthermore, our results distinguished phenotypes of homozygosity and heterozygosity of the SAAV presence through direct concentration level characterization. These findings provide some insights into how SAAVs affect quantitative assessments of target peptides. The assay demonstrates a platform for proteogenomic analyses with potential applications in both research and clinical settings.

genetics↗
DOE OSTI2021

Fast and accurate metagenotyping of the human gut microbiome with GT-Pro

Single nucleotide polymorphisms (SNPs) in metagenomics are used to quantify population structure, track strains and identify genetic determinants of microbial phenotypes. However, existing alignment-based approaches for metagenomic SNP detection require high-performance computing and enough read coverage to distinguish SNPs from sequencing errors. To address these issues, we developed the GenoTyper for Prokaryotes (GT-Pro), a suite of methods to catalog SNPs from genomes and use unique k-mers to rapidly genotype these SNPs from metagenomes. Compared to methods that use read alignment, GT-Pro is more accurate and two orders of magnitude faster. Here, using high-quality genomes, we constructed a catalog of 104 million SNPs in 909 human gut species and used unique k-mers targeting this catalog to characterize the global population structure of gut microbes from 7,459 samples. GT-Pro enables fast and memory-efficient metagenotyping of millions of SNPs on a personal computer.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A genomic data archive from the Network for Pancreatic Organ donors with Diabetes

The Network for Pancreatic Organ donors with Diabetes (nPOD) is the largest biorepository of human pancreata and associated immune organs from donors with type 1 diabetes (T1D), maturity-onset diabetes of the young (MODY), cystic fibrosis-related diabetes (CFRD), type 2 diabetes (T2D), gestational diabetes, islet autoantibody positivity (AAb+), and without diabetes. nPOD recovers, processes, analyzes, and distributes high-quality biospecimens, collected using optimized standard operating procedures, and associated de-identified data/metadata to researchers around the world. Herein describes the release of high-parameter genotyping data from this collection. 372 donors were genotyped using a custom precision medicine single nucleotide polymorphism (SNP) microarray. Data were technically validated using published algorithms to evaluate donor relatedness, ancestry, imputed HLA, and T1D genetic risk score. Additionally, 207 donors were assessed for rare known and novel coding region variants via whole exome sequencing (WES). These data are publicly-available to enable genotype-specific sample requests and the study of novel genotype:phenotype associations, aiding in the mission of nPOD to enhance understanding of diabetes pathogenesis to promote the development of novel therapies.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Sub genome anchored physical frameworks of the allotetraploid Upland cotton (Gossypium hirsutum L.) genome, and an approach toward reference-grade assemblies of polyploids

Like those of many agricultural crops, the cultivated cotton is an allotetraploid and has a large genome (~2.5 gigabase pairs). The two sub genomes, A and D, are highly similar but unequally sized and repeat-rich, which pose significant challenges for accurate genome reconstruction using standard approaches. Here we report the development of BAC libraries, sub genome specific physical maps, and a new-generation sequencing approach that will lead to a reference-grade genome assembly for Upland cotton. Three BAC libraries were constructed, fingerprinted, and integrated with BAC-end sequences (BES) to produce a de novo whole-genome physical map. The BAC map was partitioned by sub genomes through alignment to the diploid progenitor D-genome reference sequence with densely spaced BES anchor points and computational filtering. The physical maps were validated with FISH and genetic mapping of SNP markers derived from BES. Two pairs of homeologous chromosomes, A11/D11 and A12/D12, were used to assess multiplex sequencing approaches for completeness and scalability. The results represent the first sub genome anchored physical maps of Upland cotton, and a new-generation approach to the whole-genome sequencing, which will lead to the reference-grade assembly of allopolyploid cotton and serve as a general strategy for sequencing other polyploid species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Genome-wide association analysis of the strength of the MAMP-elicited defense response and resistance to target leaf spot in sorghum

Abstract Plants have the capacity to respond to conserved molecular features known as microbe-associated molecular patterns (MAMPs). The goal of this work was to assess variation in the MAMP response in sorghum, to map loci associated with this variation, and to investigate possible connections with variation in quantitative disease resistance. Using an assay that measures the production of reactive oxygen species, we assessed variation in the MAMP response in a sorghum association mapping population known as the sorghum conversion population (SCP). We identified consistent variation for the response to chitin and flg22—an epitope of flagellin. We identified two SNP loci associated with variation in the flg22 response and one with the chitin response. We also assessed resistance to Target Leaf Spot (TLS) disease caused by the necrotrophic fungus Bipolaris cookei in the SCP. We identified one strong association on chromosome 5 near a previously characterized disease resistance gene. A moderately significant correlation was observed between stronger flg22 response and lower TLS resistance. Possible reasons for this are discussed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Visualizing novel connections and genetic similarities across diseases using a network-medicine based approach

Understanding the genetic relationships between human disorders could lead to better treatment and prevention strategies, especially for individuals with multiple comorbidities. A common resource for studying genetic-disease relationships is the GWAS Catalog, a large and well curated repository of SNP-trait associations from various studies and populations. Some of these populations are contained within mega-biobanks such as the Million Veteran Program (MVP), which has enabled the genetic classification of several diseases in a large well-characterized and heterogeneous population. Here we aim to provide a network of the genetic relationships among diseases and to demonstrate the utility of quantifying the extent to which a given resource such as MVP has contributed to the discovery of such relations. We use a network-based approach to evaluate shared variants among thousands of traits in the GWAS Catalog repository. Our results indicate many more novel disease relationships that did not exist in early studies and demonstrate that the network can reveal clusters of diseases mechanistically related. Finally, we show novel disease connections that emerge when MVP data is included, highlighting methodology that can be used to indicate the contributions of a given biobank.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Intermediate temperature fuel cells via an ion-pair coordinated polymer electrolyte

Fuel cells are attractive devices that convert chemical energy into electricity through the direct electrochemical reaction of hydrogen and oxygen. Intermediate temperature fuel cells operated at 200–300°C can simplify water and thermal managements, enable the use of non-precious or low-loading precious metal catalysts and provide insensitivity toward fuel and air impurities such as carbon monoxide. However, the performance of current intermediate temperature fuel cells is poor due to a lack of highly-conductive membrane electrolytes and optimal electrodes designed for these fuel cells. We demonstrate high-performing intermediate temperature fuel cells that use SnP 2 O 7 –polymer composite membranes and a quaternary ammonium-biphosphate ion-pair coordinated polymer electrolyte in the electrodes. The peak power density of the fuel cell under H 2 and O 2 reached 870 mW cm -2 at 240°C with minimal performance loss under exposure to 25% carbon monoxide.

30 DIRECT ENERGY CONVERSION↗
DOE OSTI2022

Pressurized formic acid dehydrogenation: an entropic spring replaces hydrogen compression cost

Formic acid is unique among liquid organic hydrogen carriers (LOHCs), because its dehydrogenation is highly entropically driven. This enables the evolution of high-pressure hydrogen at mild temperatures that is difficult to achieve with other LOHCs, conceptually by releasing the “spring” of energy stored entropically in the liquid carrier. Applications calling for hydrogen-on-demand, such as vehicle filling, require pressurized H 2 . Hydrogen compression dominates the cost for such applications, yet there are very few reports of selective, catalytic dehydrogenation of formic acid at elevated pressure. Herein, we show that homogenous catalysts with various ligand frameworks, including Noyori-type tridentate (PNP, SNS, SNP, SNPO), bidentate chelates (pyridyl)NHC, (pyridyl)phosphine, (pyridyl)sulfonamide, and their metallic precursors, are suitable catalysts for the dehydrogenation of neat formic acid under self-pressurizing conditions. Quite surprisingly, we discovered that their structural differences can be related to performance differences in their respective structural families, with some tolerant or intolerant of pressure and others that are significantly advantaged by pressurized conditions. Here, we further find important roles for H 2 and CO in catalyst activation and speciation. In fact, for certain systems, CO behaves as a healing reagent when trapped in a pressurizing reactor system, enabling extended life from systems that would be otherwise deactivated.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Deep potential generation scheme and simulation protocol for the Li 10 GeP 2 S 12 -type superionic conductors

We report solid-state electrolyte materials with superior lithium ionic conductivities are vital to the next-generation Li-ion batteries. Molecular dynamics could provide atomic scale information to understand the diffusion process of Li-ion in these superionic conductor materials. Here, we implement the deep potential generator to set up an efficient protocol to automatically generate interatomic potentials for Li 10 GeP 2 S 12 -type solid-state electrolyte materials (Li 10 GeP 2 S 12 , Li 10 SiP 2 S 12 , and Li 10 SnP 2 S 12 ). The reliability and accuracy of the fast interatomic potentials are validated. With the potentials, we extend the simulation of the diffusion process to a wide temperature range (300 K–1000 K) and systems with large size (~1000 atoms). Important technical aspects such as the statistical error and size effect are carefully investigated, and benchmark tests including the effect of density functional, thermal expansion, and configurational disorder are performed. The computed data that consider these factors agree well with the experimental results, and we find that the three structures show different behaviors with respect to configurational disorder. Our work paves the way for further research on computation screening of solid-state electrolyte materials.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Accelerating flux balance calculations in genome-scale metabolic models by localizing the application of loopless constraints

Abstract Background Genome-scale metabolic network models and constraint-based modeling techniques have become important tools for analyzing cellular metabolism. Thermodynamically infeasible cycles (TICs) causing unbounded metabolic flux ranges are often encountered. TICs satisfy the mass balance and directionality constraints but violate the second law of thermodynamics. Current practices involve implementing additional constraints to ensure not only optimal but also loopless flux distributions. However, the mixed integer linear programming problems required to solve become computationally intractable for genome-scale metabolic models. Results We aimed to identify the fewest needed constraints sufficient for optimality under the loopless requirement. We found that loopless constraints are required only for the reactions that share elementary flux modes representing TICs with reactions that are part of the objective function. We put forth the concept of localized loopless constraints (LLCs) to enforce this minimal required set of loopless constraints. By combining with a novel procedure for minimal null-space calculation, the computational time for loopless flux variability analysis (ll-FVA) is reduced by a factor of 10–150 compared to the original loopless constraints and by 4–20 times compared to the current fastest method Fast-SNP with the percent improvement increasing with model size. Importantly, LLCs offer a scalable strategy for loopless flux calculations for multi-compartment/multi-organism models of large sizes, for example, shortening the CPU time for ll-FVA from 35 h to less than 2 h for a model with more than104 reactions. Availability and implementation Matlab functions are available in the Supplementary Material or at https://github.com/maranasgroup/lll-FVA Supplementary information Supplementary data are available at Bioinformatics online.

Chan, Siu H. J. (ORCID:000000027707656X)↗
DOE OSTI2021

NLR diversity and candidate fusiform rust resistance genes in loblolly pine

Resistance to fusiform rust disease in loblolly pine (Pinus taeda) is a classic gene-for-gene system. Early resistance gene mapping in the P. taeda family 10-5 identified RAPD markers for a major fusiform rust resistance gene, Fr1. More recently, single nucleotide polymorphism (SNP) markers associated with resistance were mapped to a full-length gene model in the loblolly pine genome encoding for a nucleotide-binding site leucine-rich repeat (NLR) protein. NLR genes are one of the most abundant gene families in plant genomes and are involved in effector-triggered immunity. Inter- and intraspecies studies of NLR gene diversity and expression have resulted in improved disease resistance. To characterize NLR gene diversity and discover potential resistance genes, we assembled de novo transcriptomes from 92 loblolly genotypes from across the natural range of the species. In these transcriptomes, we identified novel NLR transcripts that are not present in the loblolly pine reference genome and found significant geographic diversity of NLR genes providing evidence of gene family evolution. We designed capture probes for these NLRs to identify and map SNPs that stably cosegregate with resistance to the SC20-21 isolate of Cronartium quercuum f.sp. fusiforme (Cqf) in half-sib progeny of the 10-5 family. We identified 10 SNPs and 2 quantitative trait loci associated with resistance to SC20-21 Cqf. The geographic diversity of NLR genes provides evidence of NLR gene family evolution in loblolly pine. The SNPs associated with rust resistance provide a resource to enhance breeding and deployment of resistant pine seedlings.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

MINE: maximally informative next experiment—toward a new GWAS experimental design and methodology

Abstract The computational methodology of Genome Wide Association Studies (GWAS) currently has several limitations: (i) the number of observations (rows) on a quantitative trait tends to be smaller than the number of single nucleotide polymorphisms (SNPs) (columns) in the design matrix; (ii) each SNP is usually modeled separately, failing to acknowledge interaction between each other (ie epistasis); (iii) there is implicit linkage disequilibrium (LD) between neighboring SNPs due to their linkage. To overcome these issues, we developed a tool that uses ensemble methods to fit mixed linear models to GWAS data, and these ensemble methods include the development of a new experimental design approach in GWAS, which uses the resultant models and data to select the next informative experiment over time. This new adaptive and staged approach for GWAS experimental design was developed and tested in a 3 yr adaptive model-guided discovery experiment against a fixed classical design. In Sorghum bicolor a total of 79, 86, and 78 accessions were tested in years 1, 2, and 3, respectively out of 343 accessions available in the Bioenergy Association Panel (BAP) each identified for 232,303 SNPs, 1 every 2–3 kb in the genomes. We demonstrated the feasibility of MINE enacted with 8 people in the field per year over 3 yr vs in 1 large classical design enacted with 20 people in 1 yr. The MINE results for chromosomal regions identified controlling dry weight were confirmed against results from previous sorghum GWAS experiments and 1 large classical design for the BAP panel.

Genetics & Heredity↗