Genome-wide association of dry (Tamar) date palm fruit color.

Date palm (Phoenix dactylifera) fruit (dates) are an economically and culturally significant crop in the Middle East and North Africa. There are hundreds of different commercial cultivars producing dates with distinctive shapes, colors, and sizes. Genetic studies of some date palm traits have been performed, including sex determination, sugar content, and fresh fruit color. In this study, we used genome sequences and image data of 199 dry dates (Tamar) collected from 14 countries to identify genetic loci associated with the color of this fruit stage. Here, we find loci across multiple linkage groups (LG) associated with dry fruit color phenotype. We recover both the previously identified VIRESCENS (VIR) genotype associated with fresh fruit yellow or red color and new associations with the lightness and darkness of dry fruit. This study will add resolution to our understanding of date color phenotype, especially at the most commercially important Tamar stage.

Identifying novel interactions of the colon-cancer related APC protein with Wnt-pathway nuclear transcription factors.

BACKGROUND: Colon cancer is often driven by mutations of the adenomatous polyposis coli (APC) gene, an essential tumor suppressor gene of the Wnt ß-catenin signaling pathway. APC and its cytoplasmic interactions have been well studied. However, various groups have also observed its presence in the nucleus. Identifying novel interactions of APC in the Wnt pathway will provide an opportunity to understand APC's nuclear role better and ultimately identify potential cancer treatment targets. METHODS: We used the all-vs-all sequencing (AVA-Seq) method to interrogate the interactome of protein fragments spanning most of the 60 Wnt ß-catenin pathway proteins. Using protein fragments identified the interacting regions between the proteins with more resolution than a full-length protein approach. Pull-down assays were used to validate a subset of these interactions. RESULTS: 74 known and 703 novel Wnt ß-catenin pathway protein-protein interactions were recovered in this study. There were 8 known and 31 novel APC protein-protein interactions. Novel interactions of APC and nuclear transcription factors TCF7, JUN, FOSL1, and SOX17 were particularly interesting and confirmed in validation assays. CONCLUSION: Based on our findings of novel interactions between APC and transcription factors and previous evidence of APC localizing to the nucleus, we suggest APC may compete and repress CTNNB1. This would occur through APC binding to the transcription factors (JUN, FOSL1, TCF7) to regulate the Wnt signaling pathway including through enhanced marking of CTNNB1 for degradation in the nucleus by APC binding with SOX17. Additional novel Wnt ß-catenin pathway protein-protein interactions from this study could lead researchers to novel drug designs for cancer.

Application of human RNase P normalization for the realistic estimation of SARS-CoV-2 viral load in wastewater: A perspective from Qatar wastewater surveillance.

The apparent uncertainty associated with shedding patterns, environmental impacts, and sample processing strategies have greatly influenced the variability of SARS-CoV-2 concentrations in wastewater. This study evaluates the use of a new normalization approach using human RNase P for the logic estimation of SARS-CoV-2 viral load in wastewater. SARS-CoV-2 variants outbreak was monitored during the circulating wave between February and August 2021. Sewage samples were collected from five major wastewater treatment plants and subsequently analyzed to determine the viral loads in the wastewater. SARS-CoV-2 was detected in all the samples where the wastewater Ct values exhibited a similar trend as the reported number of new daily positive cases in the country. The infected population number was estimated using a mathematical model that compensated for RNA decay due to wastewater temperature and sewer residence time, and which indicated that the number of positive cases circulating in the population declined from 765,729 ± 142,080 to 2,303 ± 464 during the sampling period. Genomic analyses of SARS-CoV-2 of thirty wastewater samples collected between March 2021 and April 2021 revealed that alpha (B.1.1.7) and beta (B.1.351) were among the dominant variants of concern (VOC) in Qatar. The findings of this study imply that the normalization of data allows a more realistic assessment of incidence trends within the population.

Discovery of new therapeutic targets in ovarian cancer through identifying significantly non-mutated genes.

BACKGROUND: Mutated and non-mutated genes interact to drive cancer growth and metastasis. While research has focused on understanding the impact of mutated genes on cancer biology, understanding non-mutated genes that are essential to tumor development could lead to new therapeutic strategies. The recent advent of high-throughput whole genome sequencing being applied to many different samples has made it possible to calculate if genes are significantly non-mutated in a specific cancer patient cohort. METHODS: We carried out random mutagenesis simulations of the human genome approximating the regions sequenced in the publicly available Cancer Growth Atlas Project for ovarian cancer (TCGA-OV). Simulated mutations were compared to the observed mutations in the TCGA-OV cohort and genes with the largest deviations from simulation were identified. Pathway analysis was performed on the non-mutated genes to better understand their biological function. We then compared gene expression, methylation and copy number distributions of non-mutated and mutated genes in cell lines and patient data from the TCGA-OV project. To directly test if non-mutated genes can affect cell proliferation, we carried out proof-of-concept RNAi silencing experiments of a panel of nine selected non-mutated genes in three ovarian cancer cell lines and one primary ovarian epithelial cell line. RESULTS: We identified a set of genes that were mutated less than expected (non-mutated genes) and mutated more than expected (mutated genes). Pathway analysis revealed that non-mutated genes interact in cancer associated pathways. We found that non-mutated genes are expressed significantly more than mutated genes while also having lower methylation and higher copy number states indicating that they could be functionally important. RNAi silencing of the panel of non-mutated genes resulted in a greater significant reduction of cell viability in the cancer cell lines than in the non-cancer cell line. Finally, as a test case, silencing ANKLE2, a significantly non-mutated gene, affected the morphology, reduced migration, and increased the chemotherapeutic response of SKOV3 cells. CONCLUSION: We show that we can identify significantly non-mutated genes in a large ovarian cancer cohort that are well-expressed in patient and cell line data and whose RNAi-induced silencing reduces viability in three ovarian cancer cell lines. Targeting non-mutated genes that are important for tumor growth and metastasis is a promising approach to expand cancer therapeutic options.

Novel protein contact points among TP53 and minichromosome maintenance complex proteins 2, 3, and 5.

OBJECTIVE: Identify protein contact points between TP53 and minichromosome maintenance (MCM) complex proteins 2, 3, and 5 with high resolution allowing for potential novel Cancer drug design. METHODS: A next-generation sequencing-based protein-protein interaction method developed in our laboratory called AVA-Seq was applied to a gold-standard human protein interaction set. Proteins including TP53, MCM2, MCM3, MCM5, HSP90AA1, PCNA, NOD1, and others were sheared and ligated into the AVA-Seq system. Protein-protein interactions were then identified in both mild and stringent selective conditions. RESULTS: Known interactions among MCM2, MCM3, and MCM5 were identified with the AVA-Seq system. The interacting regions detected between these three proteins overlap with the structural data of the MCM complex, and novel domains were identified with high resolution determined by multiple overlapping fragments. Fragments of wild type TP53 were shown to interact with MCM2, MCM3, and MCM5, and details on the location of the interactions were provided. Finally, a mini-network of known and novel cancer protein interactions was provided, which could have implications for fundamental changes in multiple cancers. CONCLUSION: We provide a high-resolution mini-interactome that could direct novel drug targets and implicate possible effects of specific cancer mutations.

The QChip1 knowledgebase and microarray for precision medicine in Qatar.

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 108 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs. QChip1 had a concordance with whole-genome sequencing of 99.1%. Testing of QChip1 with 2707 Qatari genomes identified 32,674 risk variants, an average of 134 pathogenic alleles per Qatari genome. The most common pathogenic variants were those causing homocystinuria (1.12% risk allele frequency), and Stargardt disease (2.07%). The majority (85%) of Qatari SGD pathogenic variants were not present in Western populations such as European American, South Asian American, and African American in New York City and European and Afro-Caribbean in Puerto Rico; and only 50% were observed in a broad collection of data across the Greater Middle East including Kuwait, Iran, and United Arab Emirates. This study demonstrates the feasibility of developing accurate screening tools to identify SGD risk variants in understudied populations, and the need for ancestry-specific SGD screening tools.

Scaling-up a fragment-based protein-protein interaction method using a human reference interaction set.

Protein-protein interactions (PPIs) are essential in understanding numerous aspects of protein function. Here, we significantly scaled and modified analyses of the recently developed all-vs-all sequencing (AVA-Seq) approach using a gold-standard human protein interaction set (hsPRS-v2) containing 98 proteins. Binary interaction analyses recovered 20 of 47 (43%) binary PPIs from this positive reference set (PRS), comparing favorably with other methods. However, the increase of 20× in the interaction search space for AVA-Seq analysis in this manuscript resulted in numerous changes to the method required for future use in genome-wide interaction studies. We show that standard sequencing analysis methods must be modified to consider the possible recovery of thousands of positives among millions of tested interactions in a single sequencing run. The PRS data were used to optimize data scaling, auto-activator removal, rank interaction features (such as orientation and unique fragment pairs), and statistical cutoffs. Using these modifications to the method, AVA-Seq recovered >500 known and novel PPIs, including interactions between wild-type fragments of tumor protein p53 and minichromosome maintenance complex proteins 2 and 5 (MCM2 and MCM5) that could be of interest in human disease.

One Year of SARS-CoV-2: Genomic Characterization of COVID-19 Outbreak in Qatar.

Qatar, a country with a strong health system and a diverse population consisting mainly of expatriate residents, has experienced two large waves of COVID-19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global population's genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number of mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. These findings raise the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor the SARS-CoV-2 profile and re-emergence in Qatar.

Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: A nationally representative cohort study.

BACKGROUND: The epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study's objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant. METHODS AND FINDINGS: Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 individuals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic's second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented. CONCLUSIONS: In this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants.

mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar.

The SARS-CoV-2 pandemic continues to be a global health concern. The mRNA-1273 (Moderna) vaccine was reported to have an efficacy of 94.1% at preventing symptomatic COVID-19 due to infection with 'wild-type' variants in a randomized clinical trial. Here, we assess the real-world effectiveness of this vaccine against SARS-CoV-2 variants of concern, specifically B.1.1.7 (Alpha) and B.1.351 (Beta), in Qatar, a population that comprises mainly working-age adults, using a matched test-negative, case-control study design. We show that vaccine effectiveness was negligible for 2 weeks after the first dose, but increased rapidly in the third and fourth weeks immediately before administration of a second dose. Effectiveness against B.1.1.7 infection was 88.1% (95% confidence interval (CI): 83.7-91.5%) ≥14 days after the first dose but before the second dose, and was 100% (95% CI: 91.8-100.0%) ≥14 days after the second dose. Analogous effectiveness against B.1.351 infection was 61.3% after the first dose (95% CI: 56.5-65.5%) and 96.4% after the second dose (95% CI: 91.9-98.7%). Effectiveness against any severe, critical or fatal COVID-19 disease due to any SARS-CoV-2 infection (predominantly B.1.1.7 and B.1.351) was 81.6% (95% CI: 71.0-88.8%) and 95.7% (95% CI: 73.4-99.9%) after the first and second dose, respectively. The mRNA-1273 vaccine is highly effective against B.1.1.7 and B.1.351 infections, whether symptomatic or asymptomatic, and against any COVID-19 hospitalization and death, even after a single dose.

SARS-CoV-2 antibody-positivity protects against reinfection for at least seven months with 95% efficacy.

BACKGROUND: Reinfection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been documented, raising public health concerns. SARS-CoV-2 reinfections were assessed in a cohort of antibody-positive persons in Qatar. METHODS: All SARS-CoV-2 antibody-positive persons from April 16 to December 31, 2020 with a PCR-positive swab ≥14 days after the first-positive antibody test were investigated for evidence of reinfection. Viral genome sequencing was conducted for paired viral specimens to confirm reinfection. Incidence of reinfection was compared to incidence of infection in the complement cohort of those who were antibody-negative. FINDINGS: Among 43,044 antibody-positive persons who were followed for a median of 16.3 weeks (range: 0-34.6), 314 individuals (0.7%) had at least one PCR positive swab ≥14 days after the first-positive antibody test. Of these individuals, 129 (41.1%) had supporting epidemiological evidence for reinfection. Reinfection was next investigated using viral genome sequencing. Applying the viral-genome-sequencing confirmation rate, the incidence rate of reinfection was estimated at 0.66 per 10,000 person-weeks (95% CI: 0.56-0.78). Incidence rate of reinfection versus month of follow-up did not show any evidence of waning of immunity for over seven months of follow-up. Meanwhile, in the complement cohort of 149,923 antibody-negative persons followed for a median of 17.0 weeks (range: 0-45.6), incidence rate of infection was estimated at 13.69 per 10,000 person-weeks (95% CI: 13.22-14.14). Efficacy of natural infection against reinfection was estimated at 95.2% (95% CI: 94.1-96.0%). Reinfections were less severe than primary infections. Only one reinfection was severe, two were moderate, and none were critical or fatal. Most reinfections (66.7%) were diagnosed incidentally through random or routine testing, or through contact tracing. INTERPRETATION: Reinfection is rare in the young and international population of Qatar. Natural infection appears to elicit strong protection against reinfection with an efficacy ~95% for at least seven months. FUNDING: Biomedical Research Program, the Biostatistics, Epidemiology, and Biomathematics Research Core, and the Genomics Core, all at Weill Cornell Medicine-Qatar, the Ministry of Public Health, Hamad Medical Corporation, and the Qatar Genome Programme.

Evidence of Recombination Suppression Blocks on the Y Chromosome of Date Palm (Phoenix dactylifera).

The genus Phoenix includes the fruit producing date palm tree among 14 species that are all dioecious. Females produce the fruit that are high in sugar content and used in multiple countries ranging from North Africa to South Asia, especially from the Phoenix dactylifera, Phoenix sylvestris, and Phoenix canariensis species. While females produce the fruit, understanding of the genetic basis of sex control only began recently. Through genus-wide sequencing of males and females we recently identified three genes that are conserved in all males and absent in all females of the genus and confirmed an XY sex chromosome system. While our previous study focused on conservation of male-specific sequences at the genus-level, it would be of interest to better understand the spread of male-specific sequences away from the core conserved male genes on the Y chromosome during speciation. To this end, we enumerated male-specific 16 bp sequences using three male/female pairs from the western subpopulation of date palm and documented the density of these sequences in contigs of a phased date palm genome assembly. Here we show that male specific sequences in the date palm Y chromosome have likely spread in defined events that appear as blocks of varying density with significant changes in density between them. Collinearity of genes in these blocks with oil palm shows high synteny with chromosome 10 between megabase 15 and 23 and reveals that large sections of the date palm Y chromosome have maintained the ancestral structure even as recombination has stopped between X and Y.

Regulation of Circular RNA CircNFATC3 in Cancer Cells Alters Proliferation, Migration, and Oxidative Phosphorylation.

Circular RNAs were once considered artifacts of transcriptome sequencing but have recently been identified as functionally relevant in different types of cancer. Although there is still no clear main function of circRNAs, several studies have revealed that circRNAs are expressed in various eukaryotic organisms in a regulated manner often independent of their parental linear isoforms demonstrating conservation across species. circNFATC3, an abundant and uncharacterized circular RNA of exon 2 and 3 from NFATC3, was identified in transcriptomic data of solid tumors. Here we show that circNFATC3 gain- and loss-of-function experiments using RNAi-mediated circRNA silencing and circular mini vector-mediated overexpression of circularized constructs in breast and ovarian cancer cell lines affect molecular phenotypes. The knockdown of circNFATC3 induces a reduction in cell proliferation, invasion, migration, and oxidative phosphorylation. Gain-of-function of circNFATC3 in MDA-MB-231 and SK-OV-3 cells show a significant increase in cell proliferation, migration, and respiration. The above results suggest that circNFATC3 is a functionally relevant circular RNA in breast and ovarian cancer.

COVID-19 (SARS-CoV-2) outbreak monitoring using wastewater-based epidemiology in Qatar.

Raw municipal wastewater from five wastewater treatment plants representing the vast majority of the Qatar population was sampled between the third week of June 2020 and the end of August 2020, during the period of declining cases after the peak of the first wave of infection in May 2020. The N1 region of the SARS-CoV-2 genome was used to quantify the viral load in the wastewater using RT-qPCR. The trend in Ct values in the wastewater samples mirrored the number of new daily positive cases officially reported for the country, confirmed by RT-qPCR testing of naso-pharyngeal swabs. SARS-CoV-2 RNA was detected in 100% of the influent wastewater samples (7889 ± 1421 copy/L - 542,056 ± 25,775 copy/L, based on the N1 assay). A mathematical model for wastewater-based epidemiology was developed and used to estimate the number of people in the population infected with COVID-19 from the N1 Ct values in the wastewater samples. The estimated number of infected population on any given day using the wastewater-based epidemiology approach declined from 542,313 ± 51,159 to 31,181 ± 3081 over the course of the sampling period, which was significantly higher than the officially reported numbers. However, seroprevalence data from Qatar indicates that diagnosed infections represented only about 10% of actual cases. The model estimates were lower than the corrected numbers based on application of a static diagnosis ratio of 10% to the RT-qPCR identified cases, which is assumed to be due to the difficulty in quantifying RNA losses as a model term. However, these results indicate that the presented WBE modeling approach allows for a realistic assessment of incidence trend in a given population, with a more reliable estimation of the number of infected people at any given point in time than can be achieved using human biomonitoring alone.

Assessment of the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection in an Intense Reexposure Setting.

BACKGROUND: Risk of reinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We assessed the risk and incidence rate of documented SARS-CoV-2 reinfection in a cohort of laboratory-confirmed cases in Qatar. METHODS: All SARS-CoV-2 laboratory-confirmed cases with at least 1 polymerase chain reaction-positive swab that was ≥45 days after a first positive swab were individually investigated for evidence of reinfection. Viral genome sequencing of the paired first positive and reinfection viral specimens was conducted to confirm reinfection. RESULTS: Out of 133 266 laboratory-confirmed SARS-CoV-2 cases, 243 persons (0.18%) had at least 1 subsequent positive swab ≥45 days after the first positive swab. Of these, 54 cases (22.2%) had strong or good evidence for reinfection. Median time between the first swab and reinfection swab was 64.5 days (range, 45-129). Twenty-three of the 54 cases (42.6%) were diagnosed at a health facility, suggesting presence of symptoms, while 31 (57.4%) were identified incidentally through random testing campaigns/surveys or contact tracing. Only 1 person was hospitalized at the time of reinfection but was discharged the next day. No deaths were recorded. Viral genome sequencing confirmed 4 reinfections of 12 cases with available genetic evidence. Reinfection risk was estimated at 0.02% (95% confidence interval [CI], .01%-.02%), and reinfection incidence rate was 0.36 (95% CI, .28-.47) per 10 000 person-weeks. CONCLUSIONS: SARS-CoV-2 reinfection can occur but is a rare phenomenon suggestive of protective immunity against reinfection that lasts for at least a few months post primary infection.

Two prolonged viremic SARS-CoV-2 infections with conserved viral genome for two months.

We document two cases of viremic and prolonged active infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where the viral genome was conserved for two months, but infection was with little or no symptoms. The first infection persisted for 80 days and the second for 62 days. Clearance of infection occurred 40 and 41 days, respectively, after development of detectable antibodies. Both cases were identified incidentally in an investigation of reinfection in a cohort of 133,266 laboratory-confirmed infected persons.

Long non-coding RNA expression in non-obese women with polycystic ovary syndrome and weight-matched controls.

RESEARCH QUESTION: Long non-coding RNA (lncRNA) do not show protein translation but do have gene regulatory functions in several disease states. Studies have shown that lncRNA differ in overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance and hyperandrogenaemia. The objective of this study was to determine the lncRNA in serum in age- and weight-matched non-obese women with and without PCOS. METHODS: In this prospective pilot cohort study, lncRNA were measured in serum in 13 non-obese women with PCOS and 10 control women undergoing IVF. RESULTS: There was no difference between groups in terms of age, body mass index or insulin resistance. Women with PCOS showed a higher free androgen index (FAI; P = 0.03) and anti-Müllerian hormone (AMH) concentration (P = 0.001). A total of 29 lncRNA (P ≤ 0.05) differed between PCOS groups. lncRNA AC095350.1 correlated with age (r = 0.79, P = 0.04), but no correlation was seen between the significantly different lncRNA and FAI or AMH values. Functional pathway assessment using the Ingenuity Pathway Assessment tool showed no relationships for the lncRNA. CONCLUSION: lncRNA in serum differed between non-obese women with PCOS and the control group, and the pattern of expression differed from that reported in obese women with PCOS from the same ethnic population; however, it but did not correlate with androgen or insulin resistance.

Deletion of beta-fructofuranosidase (invertase) genes is associated with sucrose content in Date Palm fruit.

The fruit of date palm trees are an important part of the diet for a large portion of the Middle East and North Africa. The fruit is consumed both fresh and dry and can be stored dry for extended periods of time. Date fruits vary significantly across hundreds of cultivars identified in the main regions of cultivation. Most dried date fruit are low in sucrose but high in glucose and fructose. However, high sucrose content is a distinctive feature of some date fruit and affects flavor as well as texture and water retention. To identify the genes controlling high sucrose content, we analyzed date fruit metabolomics for association with genotype data from 120 date fruits. We found significant association of dried date sucrose content and a genomic region that contains 3 tandem copies of the beta-fructofuranosidase (invertase) gene in the reference Khalas genome, a low-sucrose fruit. High-sucrose cultivars including the popular Deglet Noor had a homozygous deletion of two of the 3 copies of the invertase gene. We show the deletion allele is derived when compared to the ancestral allele that retains all copies of the gene in 3 other species of Phoenix. The fact that 2 of the 3 tandem invertase copies are associated with dry fruit sucrose content will assist in better understanding the distinct roles of multiple date palm invertases in plant physiology. Identification of the recessive alleles associated with end-point sucrose content in date fruit may be used in selective breeding in the future.

Epigenetics meets proteomics in an epigenome-wide association study with circulating blood plasma protein traits.

DNA methylation and blood circulating proteins have been associated with many complex disorders, but the underlying disease-causing mechanisms often remain unclear. Here, we report an epigenome-wide association study of 1123 proteins from 944 participants of the KORA population study and replication in a multi-ethnic cohort of 344 individuals. We identify 98 CpG-protein associations (pQTMs) at a stringent Bonferroni level of significance. Overlapping associations with transcriptomics, metabolomics, and clinical endpoints suggest implication of processes related to chronic low-grade inflammation, including a network involving methylation of NLRC5, a regulator of the inflammasome, and associated pQTMs implicating key proteins of the immune system, such as CD48, CD163, CXCL10, CXCL11, LAG3, FCGR3B, and B2M. Our study links DNA methylation to disease endpoints via intermediate proteomics phenotypes and identifies correlative networks that may eventually be targeted in a personalized approach of chronic low-grade inflammation.