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PubMed2005

DArT for high-throughput genotyping of Cassava (Manihot esculenta) and its wild relatives.

Understanding the distribution of genetic diversity within and among individuals, populations, species and gene pools is crucial for the efficient management of germplasm collections. Molecular markers are playing an increasing role in germplasm characterization, yet their broad application is limited by the availability of markers, the costs and the low throughput of existing technologies. This is particularly true for crops of resource-poor farmers such as cassava, Manihot esculenta. Here we report on the development of Diversity Arrays Technology (DArT) for cassava. DArT uses microarrays to detect DNA polymorphism at several hundred genomic loci in a single assay without relying on DNA sequence information. We tested three complexity reduction methods and selected the two that generated genomic representations with the largest frequency of polymorphic clones (PstI/TaqI: 14.6%, PstI/BstNI: 17.2%) to produce large genotyping arrays. Nearly 1,000 candidate polymorphic clones were detected on the two arrays. The performance of the PstI/TaqI array was validated by typing a group of 38 accessions, 24 of them in duplicate. The average call rate was 98.1%, and the scoring reproducibility was 99.8%. DArT markers displayed fairly high polymorphism information content (PIC) values and revealed genetic relationships among the samples consistent with the information available on these samples. Our study suggests that DArT offers advantages over current technologies in terms of cost and speed of marker discovery and analysis. It can therefore be used to genotype large germplasm collections.

Cluster Analysis↗
PubMed2003

STRP screening sets for the human genome at 5 cM density.

BACKGROUND: Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density. RESULTS: We report the development of two separate 10 cM human STRP Screening Sets (Sets 12 and 52) which span all chromosomes. When combined, the two Sets contain a total of 782 STRPs, with average STRP spacing of 4.8 cM, average heterozygosity of 0.72, and total sex-average coverage of 3535 cM. The current Sets are comprised almost entirely of STRPs based on tri- and tetranucleotide repeats. We also report correction of primer sequences for many STRPs used in previous Screening Sets. Detailed information for the new Screening Sets is available from our web site: http://research.marshfieldclinic.org/genetics. CONCLUSION: Our new human STRP Screening Sets will improve the quality and cost effectiveness of genotyping for gene mapping and other applications.

Base Sequence↗
PubMed2000

Antigenic equivalence of human T-cell responses to Mycobacterium tuberculosis-specific RD1-encoded protein antigens ESAT-6 and culture filtrate protein 10 and to mixtures of synthetic peptides.

The early secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10) are promising antigens for reliable immunodiagnosis of tuberculosis. Both antigens are encoded by RD1, a genomic region present in all strains of Mycobacterium tuberculosis and M. bovis but lacking in all M. bovis bacillus Calmette-Guérin vaccine strains. Production and purification of recombinant antigens are laborious and costly, precluding rapid and large-scale testing. Aiming to develop alternative diagnostic reagents, we have investigated whether recombinant ESAT-6 (rESAT-6) and recombinant CFP-10 (rCFP-10) can be replaced with corresponding mixtures of overlapping peptides spanning the complete amino acid sequence of each antigen. Proliferation of M. tuberculosis-specific human T-cell lines in response to rESAT-6 and rCFP-10 and that in response to the corresponding peptide mixtures were almost completely correlated (r = 0.96, P < 0.0001 for ESAT-6; r = 0.98, P < 0.0001 for CFP-10). More importantly, the same was found when gamma interferon production by peripheral blood mononuclear cells in response to these stimuli was analyzed (r = 0.89, P < 0.0001 for ESAT-6; r = 0.89, P < 0.0001 for CFP-10). Whole protein antigens and the peptide mixtures resulted in identical sensitivity and specificity for detection of infection with M. tuberculosis. The peptides in each mixture contributing to the overall response varied between individuals with different HLA-DR types. Interestingly, responses to CFP-10 were significantly higher in the presence of HLA-DR15, which is the major subtype of DR2. These results show that mixtures of synthetic overlapping peptides have potency equivalent to that of whole ESAT-6 and CFP-10 for sensitive and specific detection of infection with M. tuberculosis, and peptides have the advantage of faster production at lower cost.

Antigens, Bacterial↗
PubMed2026

Circulating Tumor DNA in Breast Cancer: A Liquid Biopsy Revolution for Non-Invasive Genomic Profiling and Clinical Decision-Making.

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women worldwide, underscoring the need for accurate, minimally invasive biomarkers to support precision oncology. Conventional tissue biopsy remains the standard for molecular characterization but is limited by its invasiveness, inability to capture spatial and temporal tumor heterogeneity, and challenges in serial monitoring. Circulating tumor DNA (ctDNA), a tumor-derived fraction of cell-free DNA, has emerged as a promising liquid biopsy biomarker capable of providing real-time genomic information throughout disease progression. This narrative review examines recent advances in ctDNA biology, analytical technologies, clinical applications, current limitations, and future directions in breast cancer management. A structured literature search of PubMed/MEDLINE, Scopus, Embase, Web of Science, and Google Scholar identified relevant English-language publications from 2015 to 2026. Current evidence indicates that highly sensitive platforms, including digital PCR, BEAMing, and next-generation sequencing, can detect clinically actionable alterations in genes such as PIK3CA, ESR1, TP53, ERBB2, AKT1, and BRCA1/2. ctDNA has demonstrated particular utility in identifying minimal residual disease, monitoring therapeutic response, detecting emerging resistance mechanisms, and guiding targeted treatment selection in advanced breast cancer. However, applications in early cancer detection, population screening, and artificial intelligence-assisted clinical decision-making remain investigational. Widespread clinical implementation is constrained by low ctDNA abundance in early-stage disease, analytical variability, limited assay standardization, and cost considerations. Continued technological innovation, prospective multicenter validation, standardized testing protocols, and evidence-based clinical guidelines are essential to fully integrate ctDNA into routine precision breast cancer care.

breast cancer↗
PubMed1992

Rationale for an integrated approach to genetic epidemiology.

CONCLUSION: Genetic knowledge is now in the public domain and its interpretation by the media and the citizens brings the issues into the public forum of discussion for the necessary ethical, legal and socio-cultural evaluation of its application. Science is being perceived by some as dangerous and as requiring international regulation. Others feel that genetic knowledge will be the breakthrough that will permit medical progress and individual autonomy with regards to personal health and lifestyle choices. The mapping of the human genome has already yielded valuable information on an increasing number of diseases and their variants. Prevailing popular and journalistic archetypes ("imaginaires") used in the media are perceived by the producers as slowing down the possible application of genetic knowledge. The answers to these dilemmas are not readily apparent nor are they prescribed by classical philosophy of medicine. Since genetic knowledge eventually resides with the individual who carries the genes of disease and/or susceptibility, a logical approach to integration of this knowledge at a societal level would seem to reside with individual education and decision-making. The politics of the ensuing social debate could transform the current social contract since an individual's interests need to be balanced against those of his or her immediate family in the sharing of information. The ethical foundations of such a contract requires the genetic education of "Everyone" as a matter of urgent priority. Genetic education should not serve ideological power struggles between the medical establishment and the ethical-legal alliance. Instead, it should ensure the transfer of knowledge to physicians, to patients, to users, to planners, to social science and humanities researchers and to politicians, so that they may make "informed" and free decisions....

Base Sequence↗
PubMed2006

Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations.

PURPOSE: Traditional genetic approaches to identify gene mutations in cancer are expensive and laborious. Nonetheless, if we are to avoid rejecting effective molecular targeted therapies, we must test these drugs in patients whose tumors harbor mutations in the drug target. We hypothesized that gene expression profiling might be a more rapid and cost-effective method of identifying tumors that contain specific genetic abnormalities. MATERIALS AND METHODS: Gene expression profiles of 46 samples of medulloblastoma were generated using the U133av2 Affymetrix oligonucleotide array and validated using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Genetic abnormalities were confirmed using fluorescence in situ hybridization (FISH) and direct sequencing. RESULTS: Unsupervised analysis of gene expression profiles partitioned medulloblastomas into five distinct subgroups (subgroups A to E). Gene expression signatures that distinguished these subgroups predicted the presence of key molecular alterations that we subsequently confirmed by gene sequence analysis and FISH. Subgroup-specific abnormalities included mutations in the Wingless (WNT) pathway and deletion of chromosome 6 (subgroup B) and mutations in the Sonic Hedgehog (SHH) pathway (subgroup D). Real-time RT-PCR analysis of gene expression profiles was then used to predict accurately the presence of mutations in the WNT and SHH pathways in a separate group of 31 medulloblastomas. CONCLUSION: Genome-wide expression profiles can partition large tumor cohorts into subgroups that are enriched for specific genetic alterations. This approach may assist ultimately in the selection of patients for future clinical trials of molecular targeted therapies.

Adolescent↗
PubMed2007

Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of cardiovascular diseases.

PURPOSE: Long QT Syndrome, Marfan Syndrome, hypertrophic and dilated cardiomyopathy are caused by mutations in large, multi-exon genes that are principally expressed in cardiovascular tissues. Genetic testing for these disorders is labor-intensive and expensive. We sought to develop a more rapid, comprehensive, and cost-effective approach. METHODS: Paired whole blood samples were collected into tubes with or without an RNA-preserving solution, and harvested for whole blood RNA or leukocyte DNA, respectively. Large overlapping cDNA fragments from KCNQ1 and KCNH2 (Long QT Syndrome), MYBPC3 (hypertrophic and dilated cardiomyopathy), or FBN1 (Marfan Syndrome) were amplified from RNA and directly sequenced. Variants were confirmed in leukocyte DNA. RESULTS: All 4 transcripts were amplified and sequenced from whole blood mRNA. Six known and 2 novel mutations were first identified from RNA of 10 probands, and later confirmed in genomic DNA, at considerable savings in time and cost. In one patient with MFS, RNA sequencing directly identified a splicing mutation. Results from RNA and DNA were concordant for single nucleotide polymorphisms at the same loci. CONCLUSION: Taking advantage of new whole blood RNA stabilization methods, we have designed a cost-effective, comprehensive method for mutation detection that should significantly facilitate clinical genetic testing in four lethal cardiovascular disorders.

Adolescent↗
PubMed2006

Expression genetics and the phenotype revolution.

Genetic analysis of variation demands large numbers of individuals and even larger numbers of genotypes. The identification of alleles associated with Mendelian disorders has involved sample sizes of a thousand or more. Pervasive and common diseases that afflict human populations--cancer, heart disease, diabetes, neurodegeneration, addiction--are all polygenic and are even more demanding of large numbers. DeCode Genetics (http://www.decode.com) has harnessed the human resources of Iceland to unravel genetic and molecular causes of complex disease. The UK BioBank project (http://www.ukbiobank.ac.uk/) will incorporate 500,000 adult volunteers. The murine Collaborative Cross is the experimental equivalent of these human populations and will consist of a panel of approximately 1000 recombinant strains, expandable by intercrossing to much larger numbers of isogenic but heterozygous F(1)s. Massive projects of these types require efficient technologies. We have made enormous progress on the genotyping front, and it is now important to focus energy on devising ultrahigh-throughput methods to phenotype. Molecular phenotyping of the transcriptome has matured, and it is now possible to acquire hundreds of thousands of mRNA phenotypes at a cost matching those of SNPs. Proteomic and cell-based assays are also maturing rapidly. The acquisition of a personal genome along with a personal molecular phenome will provide an effective foundation for personalized medicine. Rodent models will be essential to test our ability to predict susceptibility and disease outcome using SNP data, molecular phenomes, and environmental exposures. These models will also be essential to test new treatments in a robust systems context that accounts for genetic variation.

Animals↗
PubMed1999

Nucleic acid based techniques for the detection of rare cancer cells in clinical samples.

Solid tumors evolve from cells which have lost control functions safeguarding their genomic integrity by mutation within specific genes. Consequently, proliferating cells within a tumor differ slightly from generation to generation. This permits the continuous production of new and subsequent selection of the best adapted cells, which retain this capacity of self-evolution. The threat of neoplastic diseases is due to the clinical experience, that surgical resection of all cells with this potential for autonomous evolution is often not achievable, since they were spread to distant non-resectable sites in the organism before diagnosis and surgical removal of the primary tumor and might later grow out as metastatic lesion. Lack of diagnostic techniques to detect small preneoplastic lesions as well as single spread cancer cells often causes delayed diagnosis when curative therapy is no longer achievable. Recent advances in characterizing the molecular basis of genomic instability, identifying specific gatekeeper mutations and their functional consequences in neoplastic cells now permit the development of new highly sensitive tests to identify preneoplastic lesions as well as spread single cancer cells. These techniques carry a tremendous potential for simple cost effective cancer early detection and screening assays as well as for diagnostic applications to identify spread cancer cells. Thus, they most likely will soon guide indication for surgical and adjuvant therapy protocols for patients with preneoplastic or neoplastic lesions. However, due to the complexity of the assays and the great variety of technical aspects involved almost all diagnostic applications are not yet standardized. This poses significant problems for quality control as well as inter-laboratory comparability of the results and underlines the urgent demand for well controlled collaborative efforts to evaluate indications and diagnostic standards for these assays. Here, the theoretical background, basic principles and some diagnostic applications of these new tests are reviewed.

Animals↗
PubMed1998

Ethical and legal issues.

This article considers the general issues surrounding screening, in particular the problems involved in the collection and use of information derived from screening. Different forms of screening entail particular problems, which have their own ethical complexities. The legal and ethical issues arising from screening are likely to assume greater significance. The screening opportunities afforded by the Human Genome Project will provide humanity with choices that would have been inconceivable to any previous generation.

Ethics, Medical↗
PubMed2003

Metabolic biomarker and kinase drug target discovery in cancer using stable isotope-based dynamic metabolic profiling (SIDMAP).

Tumor cells respond to growth signals by the activation of protein kinases, altered gene expression and significant modifications in substrate flow and re-distribution among biosynthetic pathways. This results in a proliferating phenotype with altered cellular function. These transformed cells exhibit unique anabolic characteristics, which includes increased and preferential utilization of glucose through the non-oxidative steps of the pentose cycle for nucleic acid synthesis but limited de novo fatty acid synthesis and TCA cycle glucose oxidation. This primarily non-oxidative anabolic profile reflects an undifferentiated highly proliferative aneuploid cell phenotype and serves as a reliable metabolic biomarker to determine cell proliferation rate and the level of cell transformation/differentiation in response to drug treatment. Novel drugs effective in particular cancers exert their anti-proliferative effects by inducing significant reversions of a few specific non-oxidative anabolic pathways. Here we present evidence that cell transformation of various mechanisms is sustained by a unique disproportional substrate distribution between the two branches of the pentose cycle for nucleic acid synthesis, glycolysis and the TCA cycle for fatty acid synthesis and glucose oxidation. This can be demonstrated by the broad labeling and unique specificity of [1,2-(13)C(2)]glucose to trace a large number of metabolites in the metabolome. Stable isotope-based dynamic metabolic profiles (SIDMAP) serve the drug discovery process by providing a powerful new tool that integrates the metabolome into a functional genomics approach to developing new drugs. It can be used in screening kinases and their metabolic targets, which can therefore be more efficiently characterized, speeding up and improving drug testing, approval and labeling processes by saving trial and error type study costs in drug testing.

Biomarkers, Tumor↗
PubMed2004

Mutation screening of the mitochondrial genome using denaturing high-performance liquid chromatography.

Over 170 known mutations of the mitochondrial genome are responsible for disease. Due to the unique features of mitochondrial genetics, such patients are clinically diverse and difficult to diagnose. As pathogenic mitochondrial DNA (mtDNA) mutations are mostly heteroplasmic, denaturing high-performance liquid chromatography (DHPLC) could be used to detect these heteroplasmic species and therefore act as a rapid screening test for mtDNA mutations. The entire mitochondrial genome was amplified by PCR in 40 overlapping regions. In addition, known mtDNA mutants were constructed for each of these regions using a PCR-based site-directed mutagenesis approach. These mutants were used as positive controls and showed a detection limit of 3-10% heteroplasmy by DHPLC (depending on the specific mutation) compared to 40% for conventional sequencing. To further validate the screening test, mtDNA from 17 patients with seven different pathogenic mutations was used to compare mutation detection by DHPLC and conventional sequencing. DHPLC had a sensitivity of 88% compared to 82% for sequencing. This increased to 100% sensitivity for DHPLC when excluding the m.8993T>G mutation. DHPLC analysis is therefore a sensitive, rapid and cost-effective method to screen for mutations in the mitochondrial genome. The role of pyrosequencing in the quantitation of mutant load for known mtDNA mutations was highlighted using the m.3243A>G mutation as an illustrative example. Pyrosequencing analysis was able to discriminate samples containing as little as 5% heteroplasmy and proved to be an accurate and reproducible method for estimation of mutant load.

Base Sequence↗
PubMed2004

Genotyping with TaqMAMA.

TaqMAMA combines the quantitative strengths of TaqMan with the allele-specific PCR of MAMA. In this article we develop TaqMAMA as a technique for screening human DNA samples for known genetic polymorphisms. In the first set of experiments, plasmids that model all types of genetic polymorphisms were used to understand the relationship between TaqMAMA primer/template mismatches and their strength of allelic discrimination. These data can be used to improve allelic discrimination of other primer extension genotyping methodologies through directed use of nucleotide mismatches. We used the data to derive a guide for TaqMAMA primer design and DNA strand selection for TaqMAMA genotyping assays. The guide was then used to develop assays for 11 known and novel human genetic polymorphisms. Genotypes were assigned quickly and accurately in all cases. TaqMAMA genotyping assays require minimal development time, have a high probability of success, produce reliable data that are straightforward to analyze, and are very cost-competitive.

Alleles↗
PubMed2006

Quantitative analysis of SNRPN(correction of SRNPN) gene methylation by pyrosequencing as a diagnostic test for Prader-Willi syndrome and Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are 2 distinct neurodevelopmental disorders caused primarily by deficiency of specific parental contributions at an imprinted domain within the chromosomal region 15q11.2-13. In most cases, lack of paternal contribution leads to PWS either by paternal deletion (approximately 70%) or maternal uniparental disomy (UPD; approximately 30%). Most cases of AS result from the lack of a maternal contribution from this same region by maternal deletion (approximately 70%) or by paternal UPD (approximately 5%). Analysis of allelic methylation differences at the small nuclear ribonucleoprotein polypeptide N (SNRPN) locus can differentiate the maternally and paternally inherited chromosome 15 and can be used as a diagnostic test for AS and PWS. METHODS: Sodium bisulfite-treated genomic DNA was PCR-amplified for the SNRPN gene. We used pyrosequencing to individually quantify the resulting artificial C/T sequence variation at CpG sites. Anonymized DNA samples from PWS patients (n = 40), AS patients (n = 31), and controls (n = 81) were analyzed in a blinded fashion with 2 PCR and 3 pyrosequencing reactions. We compared results from the pyrosequencing assays with those obtained with a commonly used methylation-specific PCR (MS-PCR) diagnostic protocol. RESULTS: The pyrosequencing assays had a sensitivity and specificity of 100% and provided quantification of methylation at 12 CpG sites within the SNRPN locus. The resulting diagnoses were 100% concordant with those obtained from the MS-PCR protocol. CONCLUSIONS: Pyrosequencing is a rapid and robust method for quantitative methylation analysis of the SNRPN locus and can be used as a diagnostic test for PWS and AS.

Angelman Syndrome↗
PubMed1998

Overlapping genomic sequences: a treasure trove of single-nucleotide polymorphisms.

An efficient strategy to develop a dense set of single-nucleotide polymorphism (SNP) markers is to take advantage of the human genome sequencing effort currently under way. Our approach is based on the fact that bacterial artificial chromosomes (BACs) and P1-based artificial chromosomes (PACs) used in long-range sequencing projects come from diploid libraries. If the overlapping clones sequenced are from different lineages, one is comparing the sequences from 2 homologous chromosomes in the overlapping region. We have analyzed in detail every SNP identified while sequencing three sets of overlapping clones found on chromosome 5p15.2, 7q21-7q22, and 13q12-13q13. In the 200.6 kb of DNA sequence analyzed in these overlaps, 153 SNPs were identified. Computer analysis for repetitive elements and suitability for STS development yielded 44 STSs containing 68 SNPs for further study. All 68 SNPs were confirmed to be present in at least one of the three (Caucasian, African-American, Hispanic) populations studied. Furthermore, 42 of the SNPs tested (62%) were informative in at least one population, 32 (47%) were informative in two or more populations, and 23 (34%) were informative in all three populations. These results clearly indicate that developing SNP markers from overlapping genomic sequence is highly efficient and cost effective, requiring only the two simple steps of developing STSs around the known SNPs and characterizing them in the appropriate populations.

Bacteriophage P1↗
PubMed1998

Prevention of HIV transmission by blood transfusion in the developing world: achievements and continuing challenges.

In industrialized countries, the use of sensitive HIV screening tests, donor deferral, and more conservative use of blood have resulted in a dramatic decrease in the transmission of HIV infection by blood transfusion. The risk of HIV transmission in the USA by blood screened negative for HIV antibody was recently estimated at one in 440,000-660,000 donations. Despite this low risk, continued public concern has compelled blood collection agencies and policy makers to continue to search for more sensitive HIV screening tests. Genome amplification techniques are receiving increased attention and are being piloted in Germany. HIV-1 p24 antigen testing was implemented in the USA in March 1996. In the first 18 months of p24 antigen testing, an estimated 18 million blood donations were tested at a cost of US$90 million to detect three antigen-positive, antibody-negative donations. However, in many developing countries where severe anemia is widespread and the prevalence of HIV infection among blood donors is orders of magnitude greater than in industrialized countries, the blood supply is either incompletely screened or not screened at all for HIV antibody. Although the contribution of transfusion-transmitted infection to the HIV epidemic has not been accurately assessed, an estimated 5-10% of HIV infections in developing countries are due to blood transfusion. In a study conducted 1 year after implementation of HIV blood screening in the largest hospital in the capital city of the Democratic Republic of the Congo, an estimated 25% of pediatric HIV infections, and 40% of infections among children over 1 years of age, were due to transfusion. Lack of commitment by national governments and international aid organizations to this fundamental element of HIV prevention has resulted in a shortage of basic equipment, supplies, and trained personnel for blood screening. Moreover, provision of test kits alone cannot prevent HIV transmission by transfusion in resource-poor areas. More comprehensive programs are needed to improve the recruitment and retention of safe donors, essential laboratory services for blood banking and screening, technical training and supervision, appropriate use of transfusions, and the prevention of severe anemia. This article summarizes the steps being taken by developing countries to prevent HIV transmission by blood transfusion, lessons learned, and the work that still lies ahead.

Anemia↗
PubMed2025

Evaluating 12 automated, whole-genome sequencing analysis pipelines for Mycobacterium tuberculosis complex: a comparative study.

BACKGROUND: Reliance on complex, custom-built bioinformatics pipelines is a barrier to the implementation of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in high-burden settings in some low-income and middle-income countries (LMICs). Automated analysis pipelines could address this inequity in access to WGS-based diagnostics and surveillance. This study aimed to systematically evaluate the performance and usability of publicly available WGS pipelines for M tuberculosis. METHODS: We identified automated M tuberculosis WGS analysis pipelines through searches of PubMed and GitHub from database inception up to Aug 31, 2024. Accuracy, cost, accessibility, and scalability were assessed for each pipeline. We evaluated the accuracy of genotypic drug susceptibility testing (gDST) using publicly available sequences with phenotypic susceptibility data for 12 antituberculosis drugs. We estimated pooled sensitivity and specificity for each pipeline, across all drugs, by conducting a bivariate meta-analysis, with random effects representing between-drug variability. Lineage classifications were compared, and a previously epidemiologically well-characterised dataset was used to compare measures of genomic relatedness. FINDINGS: Among 28 candidate pipelines, 16 were excluded as they were unmaintained and inexecutable. 12 pipelines (11 compatible with Illumina and four compatible with Nanopore), all free to use, were included for evaluation. Six pipelines processed and stored data remotely, but for five of these six, scalability was limited by the need to upload sequences through web portals. For local processing pipelines, scalability was dependent on substantial local computational resources, data storage capacity, and command-line interfaces that limited user-friendliness. Only one of six remote-processing pipelines removed human DNA sequences before server upload. gDST was similarly accurate across ten of 11 Illumina-compatible pipelines and three of four Nanopore-compatible pipelines. All pipelines classified the main lineages consistently, although there were differences at sublineage resolution. Outputs from three of four pipelines reporting genomic relatedness were compatible with commonly cited single nucleotide polymorphism difference thresholds. INTERPRETATION: Numerous automated analysis pipelines capable of enhancing equity in M tuberculosis WGS are available. Given the overall similarities between the pipelines evaluated in this study in terms of gDST performance, lineage classification, and genomic relatedness inference, non-functional attributes such as availability, accessibility, scalability, and privacy could represent the point of difference for prospective users in LMICs with a high burden of tuberculosis. FUNDING: The Rhodes Trust, Wellcome, Ellison Institute of Technology, and the UK National Institute for Health and Care Research Oxford Biomedical Research Centre.

Mycobacterium tuberculosis↗
PubMed2006

[Frequency view on genome changes testing].

Laboratories dealing with human genome, both inherited and acquired changes, dispose with similar methods and technology. The spectrum of genetic tests is relatively broad and the number of mutations or variants tested differs substantially. Also the number of examinations carried out in individual laboratories varies. Data presented in the tables come from the year 2004 and indicate the number of examinations requested and number of positive results. Many laboratories mentioned in the registry CZDDNAL (http://www.uhkt.cz/lab_a_vysetreni/nr lab_dna_diag/dna_lab_db) perform the same tests but there is also a great number of tests carried out by only one laboratory. Reasons of the request, cost-effectiveness and clinical utility of genetic testing is being discussed.

Gene Frequency↗