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Methods in Molecular Biology (Clifton,... 2022Pharmacogenomics is an important research field that studies the impact of genetic variation of patients on drug responses, looking for correlations between single...
Pharmacogenomics is an important research field that studies the impact of genetic variation of patients on drug responses, looking for correlations between single nucleotide polymorphisms (SNPs) of patient genome and drug toxicity or efficacy. The large number of available samples and the high resolution of the instruments allow microarray platforms to produce huge amounts of SNP data. To analyze such data and find correlations in a reasonable time, high-performance computing solutions must be used. Cloud4SNP is a bioinformatics tool, based on Data Mining Cloud Framework (DMCF), for parallel preprocessing and statistical analysis of SNP pharmacogenomics microarray data.This work describes how Cloud4SNP has been extended to execute applications on Apache Spark, which provides faster execution time for iterative and batch processing. The experimental evaluation shows that Cloud4SNP is able to exploit the high-performance features of Apache Spark, obtaining faster execution times and high level of scalability, with a global speedup that is very close to linear values.
Topics: Algorithms; Computational Biology; Computing Methodologies; Genome; Humans; Microarray Analysis; Software
PubMed: 34902119
DOI: 10.1007/978-1-0716-1839-4_2 -
Prenatal Diagnosis May 2023The aim of this study was to determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to determine the diagnostic yield of exome sequencing (ES) above that of chromosomal microarray analysis (CMA) or karyotyping in fetuses with isolated fetal growth restriction (FGR). This was a systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Selected studies included those with (a) only fetuses with FGR in the absence of fetal structural anomalies and (b) negative CMA or karyotyping results. Only positive variants classified as likely pathogenic or pathogenic determined as causative of the fetal phenotype were considered. A negative CMA or karyotype result was treated as the reference standard. Eight studies with data on ES diagnostic yield, including 146 fetuses with isolated FGR, were identified. Overall, a pathogenic variant determined as potentially causative of the fetal phenotype was found in 17 cases, resulting in a 12% (95% CI: 7%-18%) incremental performance pool of ES. The vast majority were studied before 32 weeks'gestation. In conclusion, a monogenic disorder was prenatally found in association with apparently isolated FGR in 12% of these fetuses.
Topics: Pregnancy; Humans; Female; Fetal Growth Retardation; Exome Sequencing; Ultrasonography, Prenatal; Karyotyping; Microarray Analysis
PubMed: 36869857
DOI: 10.1002/pd.6339 -
Bioinformatics (Oxford, England) Apr 2020Glycan microarrays are capable of illuminating the interactions of glycan-binding proteins (GBPs) against hundreds of defined glycan structures, and have revolutionized...
MOTIVATION
Glycan microarrays are capable of illuminating the interactions of glycan-binding proteins (GBPs) against hundreds of defined glycan structures, and have revolutionized the investigations of protein-carbohydrate interactions underlying numerous critical biological activities. However, it is difficult to interpret microarray data and identify structural determinants promoting glycan binding to glycan-binding proteins due to the ambiguity in microarray fluorescence intensity and complexity in branched glycan structures. To facilitate analysis of glycan microarray data alongside protein structure, we have built the Glycan Microarray Database (GlyMDB), a web-based resource including a searchable database of glycan microarray samples and a toolset for data/structure analysis.
RESULTS
The current GlyMDB provides data visualization and glycan-binding motif discovery for 5203 glycan microarray samples collected from the Consortium for Functional Glycomics. The unique feature of GlyMDB is to link microarray data to PDB structures. The GlyMDB provides different options for database query, and allows users to upload their microarray data for analysis. After search or upload is complete, users can choose the criterion for binder versus non-binder classification. They can view the signal intensity graph including the binder/non-binder threshold followed by a list of glycan-binding motifs. One can also compare the fluorescence intensity data from two different microarray samples. A protein sequence-based search is performed using BLAST to match microarray data with all available PDB structures containing glycans. The glycan ligand information is displayed, and links are provided for structural visualization and redirection to other modules in GlycanStructure.ORG for further investigation of glycan-binding sites and glycan structures.
AVAILABILITY AND IMPLEMENTATION
http://www.glycanstructure.org/glymdb.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Binding Sites; Databases, Factual; Glycomics; Microarray Analysis; Polysaccharides; Proteins
PubMed: 31841142
DOI: 10.1093/bioinformatics/btz934 -
Journal of Cellular and Molecular... Jan 2021To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis...
To investigate the incidence and clinical significance of chromosomal mosaicism (CM) in prenatal diagnosis by G-banding karyotyping and chromosomal microarray analysis (CMA). This is a single-centre retrospective study of invasive prenatal diagnosis for CM. From 5758 karyotyping results and 6066 CMA results, 104 foetal cases with CM were selected and analysed further. In total, 50% (52/104) of foetal cases with CM were affected by ultrasound-detectable phenotypes. Regardless of whether they were singleton or twin pregnancies, isolated structural defects in one system (51.35%, 19/37 in singletons; 86.67%, 13/15 in twins) and a single soft marker (18.92%, 7/37 in singletons; 13.33%, 2/15 in twins) were the most common ultrasound anomalies. Mosaic autosomal trisomy (19.23%, 20/104) was the most frequent type, and its rate was higher in phenotypic foetuses (28.85%, 15/52) than in non-phenotypic foetuses (9.62%, 5/52). There was no difference in mosaic fractions between phenotypic and non-phenotypic foetuses based on specimen sources or overall classification. Discordant mosaic results were observed in 16 cases (15.38%, 16/104) from different specimens or different testing methods. Genetic counselling and clinical management regarding CM in prenatal diagnosis remain challenging due to the variable phenotypes and unclear significance. Greater caution should be used in prenatal counselling, and more comprehensive assays involving serial ultrasound examinations, different specimens or testing methods verifications and follow-up should be applied.
Topics: Adult; Genetic Counseling; Humans; Karyotype; Karyotyping; Microarray Analysis; Mosaicism
PubMed: 33201576
DOI: 10.1111/jcmm.16080 -
JAMA Neurology Dec 2022There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies report a wide range of diagnostic yields for sequence variants assessed by exome sequencing (ES) and copy number variants (CNVs) assessed by chromosomal microarray (CMA).
OBJECTIVE
To synthesize the emerging CP genetics literature and address the question of what percentage of individuals with CP have a genetic disorder via ES and CMA.
DATA SOURCES
Searched articles were indexed by PubMed with relevant queries pertaining to CP and ES/CMA (query date, March 15, 2022).
STUDY SELECTION
Inclusion criteria were as follows: primary research study, case series with 10 or more nonrelated individuals, CP diagnosis, and ES and/or CMA data used for genetic evaluation. Nonblinded review was performed.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for assessing data quality and validity. Data were extracted by a single observer.
MAIN OUTCOMES AND MEASURES
A separate meta-analysis was performed for each modality (ES, CMA). The primary outcome was proportion/molecular diagnostic yield (number of patients with a discovered genetic disorder divided by the total number of patients in the cohort), evaluated via meta-analysis of single proportions using random-effects logistic regression. A subgroup meta-analysis was conducted, using risk factor classification as a subgroup. A forest plot was used to display diagnostic yields of individual studies.
RESULTS
In the meta-analysis of ES yield in CP, the overall diagnostic yield of ES among the cohorts (15 study cohorts comprising 2419 individuals from 11 articles) was 23% (95% CI, 15%-34%). The diagnostic yield across cryptogenic CP cohorts was 35% (95% CI, 27%-45%), compared with 7% (95% CI, 4%-12%) across cohorts with known risk factors (noncryptogenic CP). In the meta-analysis of CMA yield in CP, the diagnostic yield of CMA among the cohorts (5 study cohorts comprising 294 individuals from 5 articles) was 5% (95% CI, 2%-12%).
CONCLUSIONS AND RELEVANCE
Results of this systematic review and meta-analysis suggest that for individuals with cryptogenic CP, ES followed by CMA to identify molecular disorders may be warranted.
Topics: Humans; Pathology, Molecular; Cerebral Palsy; Microarray Analysis; Exome Sequencing; DNA Copy Number Variations
PubMed: 36279113
DOI: 10.1001/jamaneurol.2022.3549 -
American Journal of Medical Genetics.... Feb 2022
Topics: Genomics; Humans; Microarray Analysis
PubMed: 35023274
DOI: 10.1002/ajmg.a.62273 -
Methods in Molecular Biology (Clifton,... 2022The aim in microarray data analysis is to discover patterns of gene expression and to identify similar genes. Simply comparing new gene sequences to known DNA sequences...
The aim in microarray data analysis is to discover patterns of gene expression and to identify similar genes. Simply comparing new gene sequences to known DNA sequences often does not reveal the function of a new gene; thus, more sophisticated techniques are in order. Nowadays, data mining techniques, and in particular the clustering process, play an important role in bioinformatics. To analyze vast amounts of data can be difficult; thus, a way to cluster similar data is needed. This chapter is devoted to illustrate the general data mining approach used in microarray data analysis, combining clustering, alignment and similarity, and to highlight a novel similarity measure capable of capturing hidden correlations between data.
Topics: Algorithms; Cluster Analysis; Computational Biology; Gene Expression Profiling; Microarray Analysis; Oligonucleotide Array Sequence Analysis
PubMed: 34902131
DOI: 10.1007/978-1-0716-1839-4_14 -
Chemical Society Reviews Mar 2024Humans and other animals produce a diverse collection of antibodies, many of which bind to carbohydrate chains, referred to as glycans. These anti-glycan antibodies are... (Review)
Review
Humans and other animals produce a diverse collection of antibodies, many of which bind to carbohydrate chains, referred to as glycans. These anti-glycan antibodies are a critical part of our immune systems' defenses. Whether induced by vaccination or natural exposure to a pathogen, anti-glycan antibodies can provide protection against infections and cancers. Alternatively, when an immune response goes awry, antibodies that recognize self-glycans can mediate autoimmune diseases. In any case, serum anti-glycan antibodies provide a rich source of information about a patient's overall health, vaccination history, and disease status. Glycan microarrays provide a high-throughput platform to rapidly interrogate serum anti-glycan antibodies and identify new biomarkers for a variety of conditions. In addition, glycan microarrays enable detailed analysis of the immune system's response to vaccines and other treatments. Herein we review applications of glycan microarray technology for serum anti-glycan antibody profiling.
Topics: Animals; Humans; Polysaccharides; Antibodies; Carbohydrates; Vaccines; Microarray Analysis
PubMed: 38305761
DOI: 10.1039/d3cs00693j -
ACS Applied Materials & Interfaces Oct 2019Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The... (Review)
Review
Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The basis for all microarray processing and fabrication is surface modification of a chip substrate and many different strategies to couple probe molecules to such substrates have been developed. We present here a critical assessment of typical biochip generation processes from a surface science point of view. While great progress has been made from a molecular biology point of view on the development of qualitative assays and impressive results have been obtained on the detection of rather low concentrations of DNA or proteins, quantitative chip-based assays are still comparably rare. We argue that lack of stable and reliable deposition chemistries has led in many cases to suboptimal quantitative reproducibility, impeded further progress in microarray development and prevented a more significant penetration of microarray technology into the diagnostic market. We suggest that surface-attached hydrogel networks might be a promising strategy to achieve highly sensitive and quantitatively reproducible microarrays.
Topics: Animals; Humans; Hydrogels; Molecular Diagnostic Techniques; Oligonucleotide Array Sequence Analysis; Protein Array Analysis; Surface Properties
PubMed: 31322854
DOI: 10.1021/acsami.9b06838 -
Genes Sep 2023(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA)...
(1) Purpose: Retrospective back-to-back comparisons were performed to evaluate the accuracy, effectiveness, and incremental yield of chromosome microarray analysis (CMA) and exome sequencing (ES) analysis in fetuses with digestive system malformations (DSMs). (2) Methods: In total, 595 women with fetal DSMs who underwent prenatal diagnosis were enrolled. We analyzed the diagnostic yields of CMA and ES and evaluated pregnancy outcomes. Copy number variants (CNVs) were classified according to the American College of Medical Genetics and Genomics guidelines. (3) Results: Pathogenic CNVs were detected in 11/517 (2.12%) fetuses, and variants of unknown significance (VUS) were identified in 69 (13.35%) fetuses using CMA. ES detected 29 pathogenic/likely pathogenic variants in 23/143 (16.08%) fetuses and 26/143 (18.2%) VUS. In those with other ultrasound abnormalities, the detection rate of multiple system structural malformations was 41.2%, followed by skeletal (33.3%), cardiovascular (25.4%), and central nervous system (18.6%) malformations. Of the 391 surviving children, 40 (10.2%) exhibited varying degrees of mental retardation. (4) Conclusion: A correlation exists between DSMs and chromosomal abnormalities. When combined with other systemic abnormalities, the incidence of chromosomal abnormalities increases significantly. Patients with congenital DSM are at risk of developing neurodevelopmental disorders. Combined CMA and ES detection of fetal DSM has good clinical application potential.
Topics: Pregnancy; Child; Humans; Female; Exome Sequencing; Retrospective Studies; Prenatal Diagnosis; Fetus; Chromosome Aberrations; Microarray Analysis; Abnormalities, Multiple; Chromosomes; Digestive System
PubMed: 37895220
DOI: 10.3390/genes14101872