Privacy in the Genomic Era

Genome sequencing technology has advanced at a rapid pace and it is now possible to generate highly-detailed genotypes inexpensively. The collection and analysis of such data has the potential to support various applications, including personalized medical services. While the benefits of the genomics revolution are trumpeted by the biomedical community, the increased availability of such data has major implications for personal privacy; notably because the genome has certain essential features, which include (but are not limited to) (i) an association with traits and certain diseases, (ii) identification capability (e.g., forensics), and (iii) revelation of family relationships. Moreover, direct-to-consumer DNA testing increases the likelihood that genome data will be made available in less regulated environments, such as the Internet and for-profit companies. The problem of genome data privacy thus resides at the crossroads of computer science, medicine, and public policy. While the computer scientists have addressed data privacy for various data types, there has been less attention dedicated to genomic data. Thus, the goal of this paper is to provide a systematization of knowledge for the computer science community. In doing so, we address some of the (sometimes erroneous) beliefs of this field and we report on a survey we conducted about genome data privacy with biomedical specialists. Then, after characterizing the genome privacy problem, we review the state-of-the-art regarding privacy attacks on genomic data and strategies for mitigating such attacks, as well as contextualizing these attacks from the perspective of medicine and public policy. This paper concludes with an enumeration of the challenges for genome data privacy and presents a framework to systematize the analysis of threats and the design of countermeasures as the field moves forward

Draft Genome Sequence of \u3cem\u3eCercospora sojina\u3c/em\u3e Isolate S9, a Fungus Causing Frogeye Leaf Spot (FLS) Disease of Soybean

Fungi are the causal agents of many of the world\u27s most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. The fungus Cercospora sojina is a plant pathogen that threatens global soybean supplies. Here, we report the genome sequence of C. sojina strain S9 and detect genome features and predicted genomic elements. The genome sequence of C. sojina is a valuable resource with potential in studying the fungal pathogenicity and soybean host resistance to frogeye leaf spot (FLS), which is caused by C. sojina. The C. sojina genome sequence has been deposited and available at DDBJ/EMBL/GenBank under the project accession number AHPQ00000000

A Comparative Genome Analysis of \u3cem\u3eCercospora sojina\u3c/em\u3e with Other Members of the Pathogen Genus \u3cem\u3eMycosphaerella\u3c/em\u3e on Different Plant Hosts

Fungi are the causal agents of many of the world\u27s most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. Here, we report the genome sequence of C. sojina, and comparative genome analysis with plant pathogen members of the genus Mycosphaerella (Zymoseptoria. tritici (synonyms M. graminicola), M. pini, M. populorum and M. fijiensis - pathogens of wheat, pine, poplar and banana, respectively). Synteny or collinearity was limited between genomes of major Mycosphaerella pathogens. Comparative analysis with these related pathogen genomes indicated distinct genome-wide repeat organization features. It suggests repetitive elements might be responsible for considerable evolutionary genomic changes. These results reveal the background of genomic differences and similarities between Dothideomycete species. Wide diversity as well as conservation on genome features forms the potential genomic basis of the pathogen specialization, such as pathogenicity to woody vs. herbaceous hosts. Through comparative genome analysis among five Dothideomycete species, our results have shed light on the genome features of these related fungi species. It provides insight for understanding the genomic basis of fungal pathogenicity and disease resistance in the crop hosts

Dissecting the Economic Impact of Soybean Diseases in the United States over Two Decades

Soybean (Glycine max L. Merrill) is an economically important commodity for United States agriculture. Nonetheless, the profitability of soybean production has been negatively impacted by soybean diseases. The economic impacts of 23 common soybean diseases were estimated in 28 soybean-producing states in the U.S., from 1996 to 2016 (the entire data set consisted of 13,524 data points). Estimated losses were investigated using a variety of statistical approaches. The main effects of state, year, pre- and post-discovery of soybean rust, region, and zones based on yield, harvest area, and production, were significant on “total economic loss” as a function of diseases. Across states and years, the soybean cyst nematode, charcoal rot, and seedling diseases were the most economically damaging diseases while soybean rust, bacterial blight, and southern blight were the least economically damaging. A significantly greater mean loss (51%) was observed in states/years after the discovery of soybean rust (2004 to 2016) compared to the pre-discovery (1996 to 2003). From 1996 to 2016, the total estimated economic loss due to soybean diseases in the U.S. was $95.48 billion, with$80.89 billion and $14.59 billion accounting for the northern and southern U.S. losses, respectively. Over the entire time period, the average annual economic loss due to soybean diseases in the U.S. reached nearly$4.55 billion, with approximately 85% of the losses occurring in the northern U.S. Low yield/harvest/production zones had significantly lower mean economic losses due to diseases in comparison to high yield/harvest/production zones. This observation was further bolstered by the observed positive linear correlation of mean soybean yield loss (in each state, due to all diseases considered in this study, across 21 years) with the mean state wide soybean production (MT), mean soybean yield (kg ha-1), and mean soybean harvest area (ha). Results of this investigation provide useful insights into how research, policy, and educational efforts should be prioritized in soybean disease management

Inhibition of Glutathione Synthesis Augments Lysis of Murine Tumor Cells by Sulhydryl-reactive Antineoplastics

A B S T R A C T GSH plays an important role in cellular defense against a wide variety of toxic electrophiles via the formation of thioether conjugates. We studied the role of GSH in murine tumor cell defense against a novel class of sulfhydryl-reactive antineoplastics, the sesquiterpene lactones (SL). Incubation of P815 mastocytoma cells with any of the four SL tested (vernolepin, helenalin, elephantopin, and eriofertopin) for 1 h resulted in 70-97% depletion of GSH. The importance of GSH resynthesis upon exposure of tumor cells to SL was evaluated with the use of buthionine sulfoximine (BSO), a selective, nontoxic inhibitor of y-glutamylcysteine synthetase. Inhibition of GSH synthesis with 0.2 mM BSO markedly enhanced SL-mediated cytolysis of four murine tumor cell lines. A 6-to 34-fold reduction in the amount of SL causing 50% lysis was obtained with BSO. Addition of BSO to P815 cells either during or immediately after a 1-h pulse with 10 ug/ml of vernolepin increased cytolysis from <3% to 78-82%. However, a 1.5-h delay in the addition of BSO to such cells, which allowed for substantial resynthesis of GSH, reduced cytolysis to 30%. Recovery of GSH synthetic capacity after BSO treatment correlated with loss of the synergistic effect of BSO on lysis by vernolepin. BSO did not augment cytolysis by six other antineoplastics (doxorubicin, mitomycin C, vinblastine, cytosine arabinoside, maytansine, and 1,3-bis-[2-chloroethyl]-1-nitrosourea [BCNU] INTRODUCTION Glutathione, the most abundant nonprotein sulfhydryl of mammalian cells, has been shown to play a critical role in cellular defense against a variety of injurious agents (1-3). We have previously studied the role of the GSH redox cycle in tumor cell defense against oxidative injury. In those studies, interference with the GSH redox cycle augmented in vitro cytolysis of tumor cells by macrophages and granulocytes as well as by a model H202-delivery system (glucose oxidase plus glucose) (4, 5). Similar manipulations enhanced the antitumor activity of H202 in vivo (6). GSH also plays a role in protection against toxic electrophiles by thioether formation. In contrast to the cyclic oxidationreduction of GSH during antioxidant defense, restoration of GSH content after detoxification of electrophiles is dependent upon its resynthesis. In this report, we consider the role of GSH and its synthesis in tumor cell defense against sulfhydryl-reactive antineoplastics, in particular, the sesquiterpene lactones (SL) We studied four SL that are active in vitro (vernolepin, helenalin, elephantopin, and eriofertopin, Biochemical assays. Total cellular glutathione (GSH plus GSSG) was measured by a minor modification of the method of Tietze as previously described (5, 28). Total glutathione is expressed as nanomoles of the tripeptide per milligram of cell protein and is referred to as GSH in this report. Extracts of cells treated with compounds that we found to cause GSH depletion were mixed with known amounts of GSH and then assayed to rule out the presence of an inhibitor of the Tietze assay, which might have accounted for the observed loss of GSH. The activity of glucose oxidase was measured with the scopoletin assay for H202 as described (29). Glutathione reductase was assayed by the method of Roos et al. (30). Protein content was determined by the method of Lowry et al. (31) using bovine serum albumin as the standard. Inhibition of glutathione synthesis with BSO. We have previously reported that with these tumors a maximal rate of GSH depletion, and thus maximal inhibition of synthesis, was achieved with 0.2 mM BSO (5). The rate of GSH depletion in the presence of BSO reflects GSH catabolism, efflux, and dilution by cell division in the absence of synthesis. BSO stock solution (20 mM in H20) was stored at 0°C for up to 3 wk before use. Cytolysis assays. Cells were labeled with Na251CrO4 as described (27). Cytolysis was studied in three experimental settings: (a) 4 X 104 labeled cells were incubated with various concentrations of lytic agent or vehicle alone (0.1-1% dimethyl sulfoxide) in the presence or absence of BSO (0.2 mM) in 0.22 ml of MEM, 5% horse serum at 37°C in 5% C02, 95% air for 18 h. (b) Cells (1.5 X 106/ml in MEM, 5% horse serum) were incubated with various concentrations of vernolepin or vehicle alone (0.1% dimethyl sulfoxide) plus Na251CrO4 for 1 h, washed extensively (four centrifugations), GSH At the indicated times (18 h for a and b, 5 h for c), supernatant (0.1 ml for a and c, 0.5 ml for b) was removed after centrifugation for gamma counting and the percent specific release was calculated as described RESULTS Depletion of tumor cell GSH by SL. The possible interaction of cellular GSH with SL was first evaluated. Incubation of P815 mastocytoma cells with vernolepin, helenalin, elephantopin, or eriofertopin for 1 h resulted in 70-97% depletion of GSH Effect of BSO on the lysis of tumor cells by SL. We evaluated the sensitivity of 51Cr-labeled tumor cells to lysis by an 18-h coincubation with SL. The synergistic interaction between BSO and vernolepin was further analyzed by considering the kinetics of onset and reversal of their effects. For this, exposure of cells to vernolepin was limited to a 1-h pulse, followed by an 18-h incubation in its absence, at which time lysis was determined

Modeling the Relationship Between Estimated Fungicide Use and Disease-Associated Yield Losses of Soybean in the United States I: Foliar Fungicides vs Foliar Diseases

Fungicide use in the United States to manage soybean diseases has increased in recent years. The ability of fungicides to reduce disease-associated yield losses varies greatly depending on multiple factors. Nonetheless, historical data are useful to understand the broad sense and long-term trends related to fungicide use practices. In the current study, the relationship between estimated soybean yield losses due to selected foliar diseases and foliar fungicide use was investigated using annual data from 28 soybean growing states over the period of 2005 to 2015. For national and regional (southern and northern United States) scale data, mixed effects modeling was performed considering fungicide use as a fixed and state and year as random factors to generate generalized R2 values for marginal (R2GLMM(m); contains only fixed effects) and conditional (R2GLMM(c); contains fixed and random effects) models. Similar analyses were performed considering soybean production data to see how fungicide use affected production. Analyses at both national and regional scales showed that R2GLMM(m) values were significantly smaller compared to R2GLMM(c) values. The large difference between R2 values for conditional and marginal models indicated that the variation of yield loss as well as production were predominantly explained by the state and year rather than the fungicide use, revealing the general lack of fit between fungicide use and yield loss/production at national and regional scales. Therefore, regression models were fitted across states and years to examine their importance in combination with fungicide use on yield loss or yield. In the majority of cases, the relationship was nonsignificant. However, the relationship between soybean yield and fungicide use was significant and positive for majority of the years in the study. Results suggest that foliar fungicides conferred yield benefits in most of the years in the study. Furthermore, the year-dependent usefulness of foliar fungicides in mitigating soybean yield losses suggested the possible influence of temporally fluctuating abiotic factors on the effectiveness of foliar fungicides and/or target disease occurrence and associated loss magnitudes

Treatment evolution in high-risk congenital diaphragmatic hernia: ten years\u27 experience with diaphragmatic agenesis.

OBJECTIVE: The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm. SUMMARY BACKGROUND DATA: CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity. METHODS: Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death or hospital discharge. RESULTS: A total of 1,569 patients with CDH were seen between January 1995 and December 2004 in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and underwent repair. The overall survival for all patients was 68%, while survival was 54% in patients with agenesis. When patients with diaphragmatic agenesis from the first 2 years were compared with similar patients from the last 2 years, there was significantly less use of ECMO (75% vs. 52%) and an increased use of inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved survival in patients with agenesis from 47% in the first 2 years to 59% in the last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital stays compared with patients without agenesis (median, 68 vs. 30 days). For the last 2 years of the study, 36% of the patients with agenesis were discharged on tube feedings and 22% on oxygen therapy. CONCLUSIONS: There has been a change in the management of infants with CDH with less frequent use of ECMO and a greater use of iNO in high-risk patients with a potential improvement in survival. However, the mortality, hospital length of stay, and morbidity in agenesis patients remain significant

Soil microbial communities in diverse agroecosystems exposed to the herbicide glyphosate

© 2020 American Society for Microbiology. Despite glyphosate\u27s wide use for weed control in agriculture, questions remain about the herbicide\u27s effect on soil microbial communities. The existing scientific literature contains conflicting results, from no observable effect of glyphosate to the enrichment of agricultural pathogens such as Fusarium spp. We conducted a comprehensive field-based study to compare the microbial communities on the roots of plants that received a foliar application of glyphosate to adjacent plants that did not. The 2-year study was conducted in Beltsville, MD, and Stoneville, MS, with corn and soybean crops grown in a variety of organic and conventional farming systems. By sequencing environmental metabarcode amplicons, the prokaryotic and fungal communities were described, along with chemical and physical properties of the soil. Sections of corn and soybean roots were plated to screen for the presence of plant pathogens. Geography, farming system, and season were significant factors determining the composition of fungal and prokaryotic communities. Plots treated with glyphosate did not differ from untreated plots in overall microbial community composition after controlling for other factors. We did not detect an effect of glyphosate treatment on the relative abundance of organisms such as Fusarium spp

Identification of Diverse Mycoviruses Through Metatranscriptomics Characterization of the Viromes of Five Major Fungal Plant Pathogens

Mycoviruses can have a marked effect on natural fungal communities and influence plant health and productivity. However, a comprehensive picture of mycoviral diversity is still lacking. To characterize the viromes of five widely dispersed plant-pathogenic fungi, Colletotrichum truncatum, Macrophomina phaseolina, Diaporthe longicolla, Rhizoctonia solani, and Sclerotinia sclerotiorum, a high-throughput sequencing-based metatranscriptomic approach was used to detect viral sequences. Total RNA and double-stranded RNA (dsRNA) from mycelia and RNA from samples enriched for virus particles were sequenced. Sequence data were assembled de novo, and contigs with predicted amino acid sequence similarities to viruses in the nonredundant protein database were selected. The analysis identified 72 partial or complete genome segments representing 66 previously undescribed mycoviruses. Using primers specific for each viral contig, at least one fungal isolate was identified that contained each virus. The novel mycoviruses showed affinity with 15 distinct lineages: Barnaviridae, Benyviridae, Chrysoviridae, Endornaviridae, Fusariviridae, Hypoviridae, Mononegavirales, Narnaviridae, Ophioviridae, Ourmiavirus, Partitiviridae, Tombusviridae, Totiviridae, Tymoviridae, and Virgaviridae. More than half of the viral sequences were predicted to be members of the Mitovirus genus in the family Narnaviridae, which replicate within mitochondria. Five viral sequences showed strong affinity with three families (Benyviridae, Ophioviridae, and Virgaviridae) that previously contained no mycovirus species. The genomic information provides insight into the diversity and taxonomy of mycoviruses and coevolution of mycoviruses and their fungal hosts