Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa.
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ABSTRACT:
SUBMITTER: Ahuno ST
PROVIDER: S-EPMC8448727 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Most pneumococci express a polysaccharide capsule, a key virulence factor and target for pneumococcal vaccines. However, pneumococci showing no serological evidence of capsule expression [nontypeable pneumococci (NTPn)] are more frequently isolated from carriage studies than in invasive disease. Limited data exist about the population structure of carriage NTPn from the African continent. We aimed to characterize carriage NTPn and compare them to previously described invasive NTPn. Carriage and invasive NTPn isolates were obtained from South African cross-sectional studies (2009 and 2012) and laboratory-based surveillance for invasive pneumococcal disease (2003-2013), respectively. Isolates were characterized by capsular locus sequence analysis, multilocus sequence typing, antimicrobial non-susceptibility patterns and phylogenetic analysis. NTPn represented 3.7 % (137/3721) of carriage isolates compared to 0.1 % (39/32 824) of invasive isolates (P<0.001), and 24 % (33/137) of individuals were co-colonized with encapsulated pneumococci. Non-susceptibility to cotrimoxazole [84 % (112/133) vs 44 % (17/39)], penicillin [77 % (102/133) vs 36 % (14/39)], erythromycin [53 % (70/133) vs 31 % (12/39)] and clindamycin [36 % (48/133) vs 18 % (7/39)] was higher (P=0.03) among carriage than invasive NTPn. Ninety-one per cent (124/137) of carriage NTPn had complete deletion of the capsular locus and 9 % (13/137) had capsule genes, compared to 44 % (17/39) and 56 % (22/39) of invasive NTPn, respectively. Carriage NTPn were slightly less diverse [Simpson's diversity index (D)=0.92] compared to invasive NTPn [D=0.97]. Sixty-seven per cent (92/137) of carriage NTPn belonged to a lineage exclusive to NTPn strains compared to 23 % (9/39) of invasive NTPn. We identified 293 and 275 genes that were significantly associated with carriage and invasive NTPn, respectively. NTPn isolates detected in carriage differed from those causing invasive disease, which may explain their success in colonisation or in causing invasive disease.
| S-EPMC6861859 | biostudies-literature
Project description:Prostate cancer (PCa) is the second most commonly diagnosed in men worldwide and one of the most frequent cancers in men in Africa. The heterogeneity of this cancer fosters the need to identify potential genetic risk factors/biomarkers. Omics variations may significantly contribute to early diagnosis and personalized treatment. However, there are few genomic studies of this disease in African populations. This review sheds light on the status of genomics research on PCa in Africa and outlines the common variants identified thus far. The allele frequencies of the most significant SNPs in Afro-native, Afro-descendants, and European populations were compared. We advocate how these few but promising data will aid in understanding, better diagnosing, and precisely treating this cancer and the need for further collaborative research on the genomics of PCa in the African continent.
| S-EPMC9593051 | biostudies-literature
Project description:Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011-2014 period. We collected sociodemographic and clinical data, and identified epidemiologic links based on person-to-person or hospital-based connections. We performed whole-genome sequencing (WGS) on the Mycobacterium tuberculosis isolates and determined pairwise single nucleotide polymorphism (SNP) differences.Among 404 participants, 123 (30%) had person-to-person or hospital-based links, leaving 281 (70%) epidemiologically unlinked. The median SNP difference between participants with person-to-person and hospital-based links was 10 (interquartile range (IQR) 8-24) and 16 (IQR 10-23), respectively. The median SNP difference between unlinked participants and their closest genomic link was 5 (IQR 3-9) and half of unlinked participants were within 7 SNPs of at least five participants.The majority of epidemiologically-unlinked XDR-TB patients had low pairwise SNP differences with at least one other participant, consistent with transmission. These data suggest that much of transmission may result from casual contact in community settings between individuals not known to one another.
| S-EPMC6195447 | biostudies-literature
Project description:High-grade serous ovarian carcinoma (HGSOC) typically remains undiagnosed until advanced stages when peritoneal dissemination has already occurred. Here, we sought to identify HGSOC-specific alterations in DNA methylation and assess their potential to provide sensitive and specific detection HGSOC at its earliest stages.
2020-08-06 | GSE155760 | GEO
Project description:PurposeHigh-grade serous ovarian carcinoma (HGSOC) typically remains undiagnosed until advanced stages when peritoneal dissemination has already occurred. Here, we sought to identify HGSOC-specific alterations in DNA methylation and assess their potential to provide sensitive and specific detection of HGSOC at its earliest stages.Experimental designMethylationEPIC genome-wide methylation analysis was performed on a discovery cohort comprising 23 HGSOC, 37 non-HGSOC malignant, and 36 histologically unremarkable gynecologic tissue samples. The resulting data were processed using selective bioinformatic criteria to identify regions of high-confidence HGSOC-specific differential methylation. Quantitative methylation-specific real-time PCR (qMSP) assays were then developed for 8 of the top-performing regions and analytically validated in a cohort of 90 tissue samples. Lastly, qMSP assays were used to assess and compare methylation in 30 laser-capture microdissected (LCM) fallopian tube epithelia samples obtained from cancer-free and serous tubal intraepithelial carcinoma (STIC) positive women.ResultsBioinformatic selection identified 91 regions of robust, HGSOC-specific hypermethylation, 23 of which exhibited an area under the receiver-operator curve (AUC) value ≥ 0.9 in the discovery cohort. Seven of 8 top-performing regions demonstrated AUC values between 0.838 and 0.968 when analytically validated by qMSP in a 90-patient cohort. A panel of the 3 top-performing genes (c17orf64, IRX2, and TUBB6) was able to perfectly discriminate HGSOC (AUC 1.0). Hypermethylation within these loci was found exclusively in LCM fallopian tube epithelia from women with STIC lesions, but not in cancer-free fallopian tubes.ConclusionsA panel of methylation biomarkers can be used to accurately identify HGSOC, even at precursor stages of the disease.
| S-EPMC6295225 | biostudies-literature
Project description:BACKGROUND:Placental mRNA was detected in maternal whole blood, raising the possibility of using maternal blood for noninvasive prenatal diagnosis. We investigated fetal mRNA detection in maternal whole blood and determined if it offered advantages over maternal plasma analysis. METHODOLOGY:The concentrations of placental expressed genes, CSH1, KISS1, PLAC4 and PLAC1 in plasma and whole blood from healthy pregnant and non-pregnant individuals were compared by real-time quantitative reverse-transcriptase polymerase chain reaction analysis. Their fetal specificity was investigated by comparing the transcript concentrations in pre- and post-delivery samples and through SNP genotyping by matrix-assisted laser-desorption and ionization time-of-flight mass spectrometry. The gene expression profiles of pregnant and non-pregnant whole blood were investigated by microarray analysis. Upregulated genes in pregnant whole blood were selected for further quantitative analysis. PRINCIPAL FINDINGS:The concentrations of the four transcripts were significantly higher in third trimester maternal whole blood than corresponding plasma without significant correlations. KISS1, PLAC4 and PLAC1 were detected in non-pregnant whole blood but not plasma. The transcripts remained detectable in some postpartum whole blood samples. The PLAC4 mRNA in maternal plasma showed fetal genotype while that in corresponding whole blood indicated both fetal and maternal contributions. Microarray analysis revealed upregulation of genes involved in neutrophil functions in pregnant whole blood including DEFA4, CEACAM8, OLFM4, ORM1, MMP8 and MPO. Though possibly pregnancy-related, they were not pregnancy-specific as suggested by the lack of post-delivery reduction in concentrations. CONCLUSIONS:Maternal plasma is preferred over maternal whole blood for placenta-derived fetal RNA detection. Most studied 'placental' mRNA molecules in maternal whole blood were of maternal origin and might be derived from processes such as 'illegitimate transcription'.
| S-EPMC2690655 | biostudies-literature
Project description:Environmental monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for research and public health purposes has grown exponentially throughout the coronavirus disease 2019 (COVID-19) pandemic. Monitoring wastewater for SARS-CoV-2 provides early warning signals of virus spread and information on trends in infections at a community scale. Indoor environmental monitoring (e.g., swabbing of surfaces and air filters) to identify potential outbreaks is less common, and the evidence for its utility is mixed. A significant challenge with surface and air filter monitoring in this context is the concern of "relic RNA," noninfectious RNA found in the environment that is not from recently deposited virus. Here, we report detection of SARS-CoV-2 RNA on surfaces in an isolation unit (a university dorm room) for up to 8 months after a COVID-19-positive individual vacated the space. Comparison of sequencing results from the same location over two time points indicated the presence of the entire viral genome, and sequence similarity confirmed a single source of the virus. Our findings highlight the need to develop approaches that account for relic RNA in environmental monitoring. IMPORTANCE Environmental monitoring of SARS-CoV-2 is rapidly becoming a key tool in infectious disease research and public health surveillance. Such monitoring offers a complementary and sometimes novel perspective on population-level incidence dynamics relative to that of clinical studies by potentially allowing earlier, broader, more affordable, less biased, and less invasive identification. Environmental monitoring can assist public health officials and others when deploying resources to areas of need and provides information on changes in the pandemic over time. Environmental surveillance of the genetic material of infectious agents (RNA and DNA) in wastewater became widely applied during the COVID-19 pandemic. There has been less research on other types of environmental samples, such as surfaces, which could be used to indicate that someone in a particular space was shedding virus. One challenge with surface surveillance is that the noninfectious genetic material from a pathogen (e.g., RNA from SARS-CoV-2) may be detected in the environment long after an infected individual has left the space. This study aimed to determine how long SARS-CoV-2 RNA could be detected in a room after a COVID-positive person had been housed there.
| S-EPMC9769851 | biostudies-literature
Project description:Neisseria meningitidis colonizes the human oropharynx and transmits mainly via asymptomatic carriage. Actual outbreaks of meningococcal meningitis are comparatively rare and occur when susceptible populations are exposed to hypervirulent clones, genetically distinct from the main carriage isolates. However, carriage isolates can evolve into pathogens through a limited number of recombination events. The present study examines the potential for the sequence type (ST)-192, by far the dominant clone recovered in recent meningococcal carriage studies in sub-Saharan Africa, to evolve into a pathogen. We used whole-genome sequencing on a collection of 478 meningococcal isolates sampled from 1- to 29-?year-old healthy individuals in Arba Minch, southern Ethiopia in 2014. The ST-192 clone was identified in nearly 60?% of the carriers. Using complementary short- and long-read techniques for whole-genome sequencing, we were able to completely resolve genomes and thereby identify genomic differences between the ST-192 carriage strain and known pathogenic clones with the highest possible resolution. We conclude that it is possible, but unlikely, that ST-192 could evolve into a significant pathogen, thus, becoming the major invasive meningococcus clone in the meningitis belt of Africa following upcoming mass vaccination with a polyvalent conjugate vaccine that targets the A, C, W, Y and X capsules.
| S-EPMC6755499 | biostudies-literature
Project description:BackgroundThe capsular polysaccharide is the principal virulence factor of Streptococcus pneumoniae and a target for current pneumococcal vaccines. However, some pathogenic pneumococci are serologically nontypeable [nontypeable pneumococci (NTPn)]. Due to their relative rarity, NTPn are poorly characterized, and, as such, limited data exist which describe these organisms. We aimed to describe disease and genotypically characterize NTPn causing invasive pneumococcal disease in South Africa.ResultsIsolates were detected through national, laboratory-based surveillance for invasive pneumococcal disease in South Africa and characterized by whole genome analysis. We predicted ancestral serotypes (serotypes from which NTPn may have originated) for Group I NTPn using multilocus sequence typing and capsular region sequence analyses. Antimicrobial resistance patterns and mutations potentially causing nontypeability were identified. From 2003-2013, 39 (0.1 %, 39/32,824) NTPn were reported. Twenty-two (56 %) had partial capsular genes (Group I) and 17 (44 %) had complete capsular deletion of which 15 had replacement by other genes (Group II). Seventy-nine percent (31/39) of our NTPn isolates were derived from encapsulated S. pneumoniae. Ancestral serotypes 1 (27 %, 6/22) and 8 (14 %, 3/22) were most prevalent, and 59 % (13/22) of ancestral serotypes were serotypes included in the 13-valent pneumococcal conjugate vaccine. We identified a variety of mutations within the capsular region of Group I NTPn, some of which may be responsible for the nontypeable phenotype. Nonsusceptibility to tetracycline and erythromycin was higher in NTPn than encapsulated S. pneumoniae.ConclusionsNTPn are currently a rare cause of invasive pneumococcal disease in South Africa and represent a genetically diverse collection of isolates.
| S-EPMC4928513 | biostudies-literature
Project description:PurposeMolecular residual disease (MRD) is the main cause of postoperative recurrence of breast cancer. However, the baseline tumor genomic characteristics and therapeutic implications of breast cancer patients with detectable MRD after surgery are still unknown.Materials and methodsIn this study, we enrolled 80 patients with breast cancer who underwent next-generation sequencing-based genetic testing of 1,021 cancer-related genes performed on baseline tumor and postoperative plasma, among which 18 patients had detectable MRD after surgery.ResultsBaseline clinical characteristics found that patients with higher clinical stages were more likely to have detectable MRD. Analysis of single nucleotide variations and small insertions/deletions in baseline tumors showed that somatic mutations in MAP3K1, ATM, FLT1, GNAS, POLD1, SPEN, and WWP2 were significantly enriched in patients with detectable MRD. Oncogenic signaling pathway analysis revealed that alteration of the Cell cycle pathway was more likely to occur in patients with detectable MRD (p=0.012). Mutational signature analysis showed that defective DNA mismatch repair and activation-induced cytidine deaminase (AID) mediated somatic hypermutation (SHM) were associated with detectable MRD. According to the OncoKB database, 77.8% (14/18) of patients with detectable MRD had U.S. Food and Drug Administration-approved mutational biomarkers and targeted therapy.ConclusionOur study reports genomic characteristics of breast cancer patients with detectable MRD. The cell cycle pathway, defective DNA mismatch repair, and AID-mediated SHM were found to be the possible causes of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.
| S-EPMC11016634 | biostudies-literature