Molecular tests predicting the risk of distant recurrence (DR) can be used to assist therapy decision-making in oestrogen receptor–positive (ER+) and human epidermal growth factor receptor 2–negative ...(HER2-) breast cancer patients after considerations of standard clinical markers. The Oncotype DX Recurrence Score (RS) is a widespread tool used for this purpose. Here, we compared the RS with the StemPrintER Risk Score (SPRS), a novel genomic predictor with a unique biological basis in its ability to measure the expression of cancer stemness genes.
We benchmarked the SPRS vs. RS, alone or in combination with clinicopathological variables expressed by the Clinical Treatment Score (CTS), for the prognostication of DR in a retrospective cohort of 776 postmenopausal patients with ER+/HER2-breast cancer enrolled in the translational arm of the randomised Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial. Likelihood ratio (LR) with χ2 test and C-index were used to assess prognostic performance for the entire ten-year follow-up period and in early (0–5 years) and late (5–10 years) intervals.
In all patients, the SPRS provided significantly more prognostic information than the RS for ten-year DR prognostication (C-index = 0.688, LR-χ2 = 33.4 vs. C-index = 0.641, LR-χ2 = 22.1) and for late (5–10 years) DR prognostication (C-index = 0.689, LR-χ2 = 18.8 vs. C-index = 0.571, LR-χ2 = 4.7). The SPRS also provided more prognostic information than the RS when added to the CTS in all patients (CTS + SPRS: LR-Δχ2 = 14.9; CTS + RS: LR-Δχ2 = 9.7) and in node-negative patients (CTS + SPRS: LR-Δχ2 = 11.7; CTS + RS: LR-Δχ2 = 6.6).
In postmenopausal ER+/HER2- breast cancer patients, SPRS provided more prognostic information than RS for DR when used alone or in combination with the CTS. The SPRS could therefore potentially identify high-risk patients, who might benefit from aggressive treatments, from low-risk patients who might safely avoid adjuvant chemotherapy or prolongation of endocrine therapy.
•The StemPrintER Risk Score (SPRS) is a stem cell–based prognostic test for breast cancer.•The SPRS was validated in ER+/HER2-postmenopausal women from the TransATAC cohort.•The SPRS was highly prognostic for early (0–5 yr) and late (5–10 yr) distant recurrence.•The SPRS was benchmarked against the Oncotype DX Breast Cancer Recurrence Score (RS).•The SPRS has the potential to help guide clinical decision-making in breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
Phenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines for
wings, a powerful genetic model ...for studying the underlying genetics for a broad range of cellular and developmental processes, are limited in speed, precision, and functional versatility. To expand on the utility of the wing as a phenotypic screening system, we developed MAPPER, an automated machine learning-based pipeline that quantifies high-dimensional phenotypic signatures, with each dimension quantifying a unique morphological feature of the
wing. MAPPER magnifies the power of
phenomics by rapidly quantifying subtle phenotypic differences in sample populations. We benchmarked MAPPER's accuracy and precision in replicating manual measurements to demonstrate its widespread utility. The morphological features extracted using MAPPER reveal variable sexual dimorphism across
species and unique underlying sex-specific differences in morphogen signaling in male and female wings. Moreover, the length of the proximal-distal axis across the species and sexes shows a conserved scaling relationship with respect to the wing size. In sum, MAPPER is an open-source tool for rapid, high-dimensional analysis of large imaging datasets. These high-content phenomic capabilities enable rigorous and systematic identification of genotype-to-phenotype relationships in a broad range of screening and drug testing applications and amplify the potential power of multimodal genomic approaches.
A novel confocal-microscopy approach for ovary volume estimation and autofluorescence control was employed to evaluate the effect of knocking down vasa-like genes in Schistosoma mansoni.
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•A novel confocal microscopy-based approach to estimate the Schistosoma mansoni ovary volume and tissue autofluorescence control.•Gene silencing of S. mansoni vasa-like gene 1 associated with a reduction in the ovary volume.•A lower number of dividing cells evident in the immature ovary of the vasa-like gene 1 knocked-down parasites.
The RNA helicase Vasa plays a pivotal role in the development of the germ line. To decipher the functional roles of vasa/PL10-like genes in the human blood fluke Schistosoma mansoni, we performed RNA interference followed by the analysis of the ovary in the adult female. Double-stranded RNA targeting the schistosome vasa-like gene Smvlg1 reduced the volume of the ovary. Changes in morphology of the ovary were analysed using carmine red-staining of the parasites followed by a novel confocal laser scanning microscopy (CLSM)-based approach to control for natural autofluorescence in female schistosome tissues. The reduction in the ovary volume may have been promoted by the loss of germ cells. By contrast, significant differences were not apparent in the number of eggs produced or hatching rate of eggs laid by the female schistosomes transfected with Smvlg1-specific dsRNA. The findings suggested a role for S. mansoni vasa/PL10-like gene -1 in germ cell development within the schistosome ovary that might impact in the pathogenesis and disease transmission by this neglected tropical disease pathogen.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
•Characteristics and challenges to goat production in South Africa are discussed.•Conventional genetic evaluations and organized breeding produced successful breeds.•Untapped genetic variation is ...found in feral and non-descript village goat populations.•Genomics can unravel the uncharacterized diversity for use in breed improvement.
Functional traits have become increasingly important for efficient breeding schemes in the goat industry due to rising costs of production relative to product prices and consumers demanding healthy and nutritious food in addition to abiding to animal welfare standards. The challenges facing South African and other developing countries’ goat industries is in the implementation of cost-effective production systems for high quality meat and milk which is safe to the consumer from communal farming regions riddled by many production challenges. Genetic improvement for economically important traits such as growth, reproduction, health and product quality is currently based on convectional estimated breeding values. These methods have been practiced for several decades for breeds benefiting from efficient breeding schemes. South Africa is one of the few countries in the world that have successfully developed high producing commercialised goat breeds some of which have been adopted in other regions. Genetic progress using conventional genetic evaluations is however lengthy and based on a few traits. Molecular and genomic tools are increasingly being used for the detection and mapping of genes of economic importance in goats. Attention is turning to the simultaneous identification of genes for production and functional traits using whole genome sequence and genome-wide SNP data. South Africa has a rich genetic pool of feral, commercial, and indigenous non-descript goat populations to select from. Preliminary studies using the Illumina Goat SNP60K bead chip have revealed high genetic diversity and uniqueness of the South African goat breeds. The unique genomes of the different breeds and populations are a potential source of genetic variation, which could be useful for genetic improvement programs. Next generation sequencing and genotyping technologies present opportunities for genomic breeding schemes in the near future. This paper reviews current challenges faced by the goat industry in South Africa and worldwide. The feasibility of using second-generation genomic tools to improve traits of economic importance in the goat industry is discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Enteric viruses (EVs) occurrence within aquatic environments varies and leads to significant risk on public health of humans, animals, and diversity of aquatic taxa. Early and efficacious recognition ...of cultivable and fastidious EVs in aquatic systems are important to ensure the sanitary level of aquatic water and implement required treatment strategies. Herein, we provided a comprehensive overview of the conventional and up-to-date eco-genomic tools for aquatic biomonitoring of EVs, aiming to develop better water pollution monitoring tools. In combination with bioinformatics techniques, genetic tools including cloning sequencing analysis, DNA microarray, next-generation sequencing (NGS), and metagenomic sequencing technologies are implemented to make informed decisions about the global burden of waterborne EVs-associated diseases. The data presented in this review are helpful to recommend that: (1) Each viral pollution detection method has its own merits and demerits; therefore, it would be advantageous for viral pollution evaluation to be integrated as a complementary platform. (2) The total viral genome pool extracted from aquatic environmental samples is a real reflection of pollution status of the aquatic eco-systems; therefore, it is recommended to conduct regular sampling through the year to establish an updated monitoring system for EVs, and quantify viral peak concentrations, viral typing, and genotyping. (3) Despite that conventional detection methods are cheaper, it is highly recommended to implement molecular-based technologies to complement aquatic ecosystems biomonitoring due to numerous advantages including high-throughput capability. (4) Continuous implementation of the eco-genetic detection tools for monitoring the EVs in aquatic ecosystems is recommended.
“Integrating China in the International Consortium for Personalized Medicine” (IC2PerMed) is a coordination and support action funded within the Horizon 2020 work program. Following the guidance of ...the International Consortium for Personalized Medicine (ICPerMed), the project’s overarching aim is to align the European Union and China’s research agendas in the field of personalized medicine (PM) to enable a swift development of PM approaches in the EU with strong leverage upon EU-Chinese collaboration. Living in the COVID-19 era, we are witnessing how the challenges imposed by the pandemic all around the globe have been acting as a catalyst for collaborations and knowledge sharing among national health systems worldwide. Given the strong interest on behalf of both Europe and China in the advancement of PM approaches, now more than ever, a cross-border collaboration between the 2 powers can accelerate the effective translation of such innovation to healthcare systems, advance research, and ensure that such change follows the directions toward the path of sustainability. IC2PerMed developments will be led by European and Chinese experts equally assembled into 3 Working Groups: (1) people and organization, (2) innovation and market, and (3) research and clinical studies in PM. This complex and dynamic network of actions thrives on dialog, cooperation, and alignment of research at national and global levels; work in the direction taken by IC2PerMed shall pave the way toward the realization of PM’s full potential, prevent it from becoming a burden for healthcare systems, and, rather, prove that it provides an essential and irreplaceable contribution to their effectiveness, efficiency, and sustainability.
Significant advances have been recently made in the development of the genetic and genomic platforms. This has greatly contributed to a better understanding of gene expression and regulation ...machinery. Consequently, this led to considerable progress in unraveling evidence of the genotype-phenotype correlation between normal/abnormal embryonic development and human disease complexity. For example, advanced genomic tools such as next-generation sequencing, and microarray-based CGH have substantially helped in the identification of gene and copy number variants associated with diseases as well as in the discovery of causal gene mutations. In addition, bioinformatic analysis tools of genome annotation and comparison have greatly aided in data analysis for the interpretation of the genetic variants at the individual level. This has unlocked potential possibilities for real advances toward new therapies in personalized medicine for the targeted treatment of human diseases. However, each of these genomic and bioinformatics tools has its limitations and hence further efforts are required to implement novel approaches to overcome these limitations. It could be possible that the use of more than one platform for genotype-phenotype deep analysis is an effective approach to disentangling the cause and treatment of the disease complexities. Our research topic aimed at deciphering these complexities by shedding some light on the recent applications of the basic and advanced genetic/genomic and bioinformatics approaches. These include studying gene-gene, protein-protein, and gene-environment interactions. We, in addition, aimed at a better understanding of the link between normal/abnormal embryonic development and the cause of human disease induction.
Rice production needs to be sustained in the coming decades, as the changeable climatic conditions are becoming more conducive to disease outbreaks. The majority of rice diseases cause enormous ...economic damage and yield instability. Among them, rice blast caused by Magnaportheoryzae is a serious fungal disease and is considered one of the major threats to world rice production. This pathogen can infect the above-ground tissues of rice plants at any growth stage and causes complete crop failure under favorable conditions. Therefore, management of blast disease is essentially required to sustain global food production. When looking at the drawback of chemical management strategy, the development of durable, resistant varieties is one of the most sustainable, economic, and environment-friendly approaches to counter the outbreaks of rice blasts. Interestingly, several blast-resistant rice cultivars have been developed with the help of breeding and biotechnological methods. In addition, 146 R genes have been identified, and 37 among them have been molecularly characterized to date. Further, more than 500 loci have been identified for blast resistance which enhances the resources for developing blast resistance through marker-assisted selection (MAS), marker-assisted backcross breeding (MABB), and genome editing tools. Apart from these, a better understanding of rice blast pathogens, the infection process of the pathogen, and the genetics of the immune response of the host plant are very important for the effective management of the blast disease. Further, high throughput phenotyping and disease screening protocols have played significant roles in easy comprehension of the mechanism of disease spread. The present review critically emphasizes the pathogenesis, pathogenomics, screening techniques, traditional and molecular breeding approaches, and transgenic and genome editing tools to develop a broad spectrum and durable resistance against blast disease in rice. The updated and comprehensive information presented in this review would be definitely helpful for the researchers, breeders, and students in the planning and execution of a resistance breeding program in rice against this pathogen.
Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large ...administrative databases using record linkage (RL) methodologies a major challenge.
We present Tucuxi-BLAST, a versatile tool for probabilistic RL that utilizes a DNA-encoded approach to encrypt, analyze and link massive administrative databases. Tucuxi-BLAST encodes the identification records into DNA. BLASTn algorithm is then used to align the sequences between databases. We tested and benchmarked on a simulated database containing records for 300 million individuals and also on four large administrative databases containing real data on Brazilian patients.
Our method was able to overcome misspellings and typographical errors in administrative databases. In processing the RL of the largest simulated dataset (200k records), the state-of-the-art method took 5 days and 7 h to perform the RL, while Tucuxi-BLAST only took 23 h. When compared with five existing RL tools applied to a gold-standard dataset from real health-related databases, Tucuxi-BLAST had the highest accuracy and speed. By repurposing genomic tools, Tucuxi-BLAST can improve data-driven medical research and provide a fast and accurate way to link individual information across several administrative databases.
Peanuts are an economically important crop cultivated worldwide. However, several limitations restrained its productivity, including biotic/abiotic stresses. CRISPR/Cas9-based gene-editing technology ...holds a promising approach to developing new crops with improved agronomic and nutritional traits. Its application has been successful in many important crops. However, the application of this technology in peanut research is limited, probably due to the lack of suitable constructs and protocols. In this study, two different constructs were generated to induce insertion/deletion mutations in the targeted gene for a loss of function study. The first construct harbors the regular gRNA scaffold, while the second construct has the extended scaffold plus terminator. The designed gRNA targeting the coding sequence of the
genes was cloned into both constructs, and their functionality and efficiency were validated using the hairy root transformation system. Both constructs displayed insertions and deletions as the types of edits. The construct harboring the extended plus gRNA terminator showed a higher editing efficiency than the regular scaffold for monoallelic and biallelic mutations. These two constructs can be used for gene editing in peanuts and could provide tools for improving peanut lines for the benefit of peanut breeders, farmers, and industry.
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