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At least 145 records · Page 8Linked to original sources
PubMed1995

The influence of maternal weight on human chorionic gonadotropin in the multiple-marker screening test for fetal Down syndrome.

OBJECTIVE: Our purpose was to determine the effect of maternal weight on human chorionic gonadotropin concentration in the multiple-marker screening test for fetal Down syndrome. STUDY DESIGN: Two genetics databases were used: database I contained the results of 8297 multiple-marker screening tests and database II contained the results of 1936 multiple-marker screening tests and fetal karyotypes. RESULTS: The overall screen-positive rate in database I was 7.1%; it was 7.5% in patients weighing < 180 pounds and 5.1% in patients weighing > or = 180 pounds (p = 0.001). Weight significantly affected the screen-positive rate only in women > or = 30 years old (p = 0.003 for 30 to 34 years, p = 0.00004 for > or = 35 years). A weight correction formula was derived; when applied to database II it eliminated individual weight-related differences but had no effect on the overall screen-positive rate or Down syndrome detection rate. CONCLUSIONS: Human chorionic gonadotropin concentration is affected by maternal weight. A weight correction formula eliminates individual weight-related differences in the screen-positive rate but has no discernible effect on the overall screen-positive or Down syndrome detection rates.

Adult↗
PubMed1995

Primary structures of three Armenian hamster monoclonal antibodies specific for idiotopes and metatopes of the monoclonal anti-fluorescein antibody 4-4-20.

This paper reports the complete V gamma, V kappa, C gamma 1 and C kappa nucleotide and deduced amino acid sequences of two hamster monoclonal anti-metatype antibodies, 3A5-1 and 4A6. These antibodies have been previously characterized in terms of their binding and molecular stabilization properties with liganded murine monoclonal and single-chain antibody 4-4-20 active sites. Also reported are the complete V kappa and C kappa nucleotide and deduced amino acid sequence of hamster monoclonal anti-idiotype antibody 1F4, which is specific for the unliganded 4-4-20 active site. Oligonucleotide primers based on the 5' ends of murine variable genes, along with primers specific for murine IgG C gamma 1 and kappa constant region genes, have been used in cDNA and polymerase chain reactions (PCRs) to amplify IgG cDNA from Armenian hamster/mouse hybridomas. The hamster C gamma 1 and C kappa domain sequences are highly homologous to previously reported murine sequences. The anti-idiotype mAb V kappa gene demonstrated strong similarity to the murine V kappa V gene subgroup while the two anti-metatype mAb V kappa genes approximated more closely to the murine V kappa III gene subgroup. The two anti-metatype mAbs utilized highly homologous V gamma genes, with differing HCDR 3 regions, that appeared similar to the murine V gamma I(a) subgroup. These sequence determinations represent the first primary structures reported for antibodies with anti-metatype activity and are additions to the relatively sparse hamster immunoglobulin genetic database. Results are discussed in terms of 4-4-20 active site specificity and anti-metatype activity, as well as immunoglobulin structural diversity in an anti-Ig immune response.

Amino Acid Sequence↗
PubMed2003

Integrating 'omic' information: a bridge between genomics and systems biology.

The availability of genome sequences for several organisms, including humans, and the resulting first-approximation lists of genes, have allowed a transition from molecular biology to 'modular biology'. In modular biology, biological processes of interest, or modules, are studied as complex systems of functionally interacting macromolecules. Functional genomic and proteomic ('omic') approaches can be helpful to accelerate the identification of the genes and gene products involved in particular modules, and to describe the functional relationships between them. However, the data emerging from individual omic approaches should be viewed with caution because of the occurrence of false-negative and false-positive results and because single annotations are not sufficient for an understanding of gene function. To increase the reliability of gene function annotation, multiple independent datasets need to be integrated. Here, we review the recent development of strategies for such integration and we argue that these will be important for a systems approach to modular biology.

Computational Biology↗
PubMed2026

Long-read Sequences Mapped to a Complete Reference Genome Uncover Uncaptured Structural Variants across the Beta-globin Cluster in Africans with Sickle Cell Disease.

African genomes are marked by extensive complexity in the number and distribution of variants, yet remain under-represented in genetic databases and the human reference genome. This gap in representation limits the broad application of genomic medicine. Sickle cell disease (SCD) - one of the most common monogenic diseases - has its highest prevalence in Africa, and variation in disease severity has consistently been linked to the beta-globin locus, including levels of fetal hemoglobin (HbF). Modulation of HbF is central to current SCD gene therapies; however, the inherent complexity and variation at the locus in African genomes presents a challenge to translating these advances to Africa. Here, we align long-read single molecule sequences (LRS) targeted to the beta-globin region to the hg38 and T2T-CHM13v2 genome references in 40 individuals with SCD, predominantly recruited from three African countries. We demonstrate that the expanded T2T-CHM13v2 reference sequence at this locus reduces Structural Variant (SV) calls by 70% and uncovers uncaptured single nucleotide variants (SNVs). Across the cluster we report 343 SVs and 196 SNVs that have not been previously reported, including in LRS data from the All of Us project. By including African populations from ethnolinguistic groups that have not been previously surveyed we improve variant resolution and bolster evidence for observed variation. Finally, we identify a common &#x223c;4kb insertion locus overlapping the HBB promoter among individuals with high HbF. These results demonstrate the utility of combining a comprehensive reference genome with LRS in African populations to uncover genomic variation at disease-associated loci.

SNV↗
PubMed2000

Ultrasound findings and multiple marker screening in trisomy 18.

OBJECTIVE: To compare detection of trisomy 18 in the second trimester by ultrasound and multiple-marker testing. METHODS: A computerized genetics database was used to identify fetuses of 14-22 weeks' gestation who had comprehensive ultrasound examinations, multiple-marker screening tests (alpha-fetoprotein [AFP]), hCG, unconjugated estriol [E3], and trisomy 18 karyotype. A positive trisomy 18 screen was defined as AFP up to 0.75 multiples of the median (MoM), hCG up to 0.55 MoM, and unconjugated E3 up to 0.60 MoM. A risk of at least 1:190 defined a positive Down syndrome screen. Ultrasound abnormalities were diagnosed prospectively and were confirmed later by retrospective review of sonographic images. RESULTS: From 1988-1997, 30 trisomy 18 fetuses who had comprehensive ultrasounds and multiple-marker testing were identified. Twenty-one (70%) had abnormalities detected by ultrasound, of which the most common isolated finding was choroid plexus cyst. Eleven fetuses (37%) had positive trisomy 18 screens, and two had positive Down syndrome screens, for a total of 13 of 30 (43%) fetuses with positive multiple-marker screening tests. CONCLUSION: We found that ultrasound was more likely to be abnormal than multiple-marker screening tests in fetuses with trisomy 18 (70%) (95% confidence interval [CI] 54, 86 versus 43% CI 25, 61). However, combining the two testing methods yielded the highest detection rate (80% [CI 66%, 94%]).

Adult↗
PubMed2002

The evolution of structural databases.

Starting with the Protein Data Bank (PDB) as a common ancestor, the evolution of structural databases has been driven by the rapprochement of the structural world and the practical applications. The result is an impressive number of secondary structural databases that is welcomed by structural biologists and bioinformaticians but runs the risk of producing an embarrassment of riches among non-specialist users. Given that any profit depends on the number of customers, efficient interfaces between many structural data banks must be available to make their contents easily accessible. Increasing the information content of central structural repositories might be the best way to guide users through the many, sometimes overlapping databases.

Computer Communication Networks↗
PubMed1998

PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity and virulence.

Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of hospital-acquired pneumonia. We identified a 73kDa protein, designated Pseudomonas exoprotein A (PepA), that was secreted by P. aeruginosa strain PA103. PepA was necessary for in vitro killing of epithelial cells as well as virulence in a mouse model of acute pneumonia. Several properties of PepA suggested that it was secreted by a type III system. Secretion occurred without cleavage of a signal peptide and in low-calcium environments in the presence of a divalent cation chelator, as is the case for characterized P. aeruginosa type III secreted proteins. Secretion of PepA was absent from isogenic mutants with defective type III pathways. Finally, amino-terminal peptide sequence analysis indicated that the amino-terminal five residues of PepA were identical to those of ExoS and ExoT, two type III secreted proteins of P. aeruginosa. After secretion, PepA underwent cleavage at two sites, each with the sequence A-X-K-S, suggesting that the cleavage may be caused by a protease. The gene encoding PepA, designated pepA, was cloned and sequenced, and comparisons with the genetic database using BLAST alignments indicated that the nucleotide sequence of pepA and the inferred protein sequence of PepA had no homology to known sequences. A nucleotide sequence identical to the consensus element for binding of ExsA, a transcriptional activator of P. aeruginosa type III secretion genes, was located 84 bp 5' of the translational start codon. Analysis of transposon insertion mutants indicated that the carboxy terminus was required for cytotoxicity. Examination of respiratory clinical isolates demonstrated that pepA was a variable trait and probably acquired by horizontal transmission. Consistent with this hypothesis was the identification of a putative insertion element 94 bp 5' of the PepA translational start site. Analysis of G + C content of the PepA coding sequence and the adjacent insertion element suggested that they were acquired together from a different species. In summary, PepA is a secreted protein of P. aeruginosa that is necessary for epithelial cell cytotoxicity in vitro and virulence in a mouse model of pneumonia.

Amino Acid Sequence↗
PubMed1997

Pregnancy outcomes following false-positive multiple marker screening tests.

Pregnancy outcomes in women with a false-positive midtrimester multiple marker screening test (MMST) were reviewed. A genetic database was used to identify all women > or = age 30 who had a MMST at 15-20 weeks of gestation, a targeted ultrasound, and amniocentesis, and complete pregnancy outcome data. All patients with an abnormal fetal ultrasound (US) or karyotype were excluded. The incidence of adverse outcomes (defined as fetal death, preterm delivery, or a birth weight less than the 10th percentile for gestational age), in those women with a positive MMST (risk of Down's syndrome > or = 1:190) was compared to the incidence of adverse outcomes in control women with negative MMST. Chi-square analysis and Fisher's exact tests were used for comparisons as appropriate. Complete data was available from 1135 women. Seventy-seven percent were over age 35. Two hundred and forty-six women (22%) had a positive multiple marker test. No significant differences in outcomes were discovered after comparisons to controls: fetal death 1 of 246 (0.4%) versus 12 of 889 (1.3%), p = 0.32; preterm delivery 32 of 246 (13.0%) versus 147 of 889 (16.5%), p = 0.17; birth weight less than the 10th percentile, 9 of 246 (3.7%) versus 30 of 889 (3.4%), p = 0.83. Our data suggest that women > or = age 30 with a false-positive MMST and a normal midtrimester obstetrical sonogram are not at an increased risk for adverse pregnancy outcomes in later gestation.

Adult↗
PubMed2001

Prenatal diagnosis from cystic hygroma fluid: the value of fluorescence in situ hybridization.

OBJECTIVE: We sought to determine the optimal approach to the prenatal chromosome analysis of cystic hygroma fluid using traditional cytogenetic analysis and fluorescence in situ hybridization. STUDY DESIGN: A retrospective evaluation of our experience with traditional cytogenetic and fluorescence in situ hybridization analysis on cystic hygroma fluid was performed through a systematic review of the Genzyme Genetics database from January 1995 to July 2000. Information on gestational age, sample volume, clinical ultrasound findings (including fetal viability), cytogenetic results, fluorescence in situ hybridization results, and turn-around-time were queried. RESULTS: Eighty-three specimens were included in the investigation. The mean gestational age was 18.1 weeks (range, 13-27 weeks), and the mean sample volume was 20.7 mL (range, 0.1-101 mL). Of the 72 samples in which > 5 mL of cystic hygroma fluid was available, the success rate for cytogenetic analysis was 76% (55/72 samples). In 11 specimens of < or = 5 mL of cystic hygroma fluid, cytogenetic analysis was successful in only 1 case (9%). Fluorescence in situ hybridization was attempted on 23 samples, 18 of which were successful (78%), including 6 of 9 cases of cell culture failure (67%). Both traditional cytogenetic analysis and fluorescence in situ hybridization were performed in 21 instances when a sample of > 5 mL was available. A successful result was obtained by either cytogenetic testing or fluorescence in situ hybridization analysis or both in 19 of 21 of these cases (90%). Samples of > 5 mL from viable fetuses had a higher cytogenetic success rate (80%) and fluorescence in situ hybridization success rate (89%) than samples from fetuses with intrauterine death (38% and 50% cytogenetic and fluorescence in situ hybridization success rates, respectively.) The mean turn-around time was 8.2 days (range, 4-17 days). Results were available in < or = 12 days in 91% of cases. There was a 91% aneuploidy rate identified, with 45,X occurring in 86% of the samples. CONCLUSION: We conclude that the optimal approach for the prenatal diagnosis of chromosome abnormalities from cystic hygroma samples is to perform both traditional cytogenetic studies and interphase prenatal fluorescence in situ hybridization evaluation for the most common aneuploidies that involve chromosomes 13, 18, 21, X, and Y. With this combined approach, our data indicate that, in viable pregnancies with a fluid sample of >5 mL, a 90% diagnostic success rate can be achieved.

Congenital Abnormalities↗
PubMed2001

Generation of a database containing discordant intron positions in eukaryotic genes (MIDB).

MOTIVATION: Intron sliding is the relocation of intron-exon boundaries over short distances and is often also referred to as intron slippage or intron migration or intron drift. We have generated a database containing discordant intron positions in homologous genes (MIDB--Mismatched Intron DataBase). Discordant intron positions are those that are either closely located in homologous genes (within a window of 10 nucleotides) or an intron position that is present in one gene but not in any of its homologs. The MIDB database aims at systematically collecting information about mismatched introns in the genes from GenBank and organizing it into a form useful for understanding the genomics and dynamics of introns thereby helping understand the evolution of genes. RESULTS: Intron displacement or sliding is critically important for explaining the present distribution of introns among orthologous and paralogous genes. MIDB allows examining of intron movements and allows mapping of intron positions from homologous proteins onto a single sequence. The database is of potential use for molecular biologists in general and for researchers who are interested in gene evolution and eukaryotic gene structure. Partial analysis of this database allowed us to identify a few putative cases of intron sliding. AVAILABILITY: http://intron.bic.nus.edu.sg/midb/midb.html

Amino Acid Sequence↗
PubMed2001

SIR: a simple indexing and retrieval system for biological flat file databases.

SUMMARY: SIR is a Simple Indexing and Retrieval tool for indexing and searching biological flat file databases. SIR is a cross-platform solution entirely written in Python. Since the package is very small and installation is trivial, this would be an ideal solution for database providers to provide a custom retrieval tool to access them. AVAILABILITY: The modules will be made available at http://www.EMBLHeidelberg.de/~chenna/PySAT/sir.html

Abstracting and Indexing↗
PubMed2002

Condition specific transcription factor binding site characterization in Saccharomyces cerevisiae.

MOTIVATION: We demonstrate a computational process by which transcription factor binding sites can be elucidated using genome-wide expression and binding profiles. The profiles direct us to the intergenic locations likely to contain the promoter regions for a given factor. These sequences are multiply and locally aligned to give an anchor motif from which further characterization can take place. RESULTS: We present bases for and assumptions about the variability within these motifs which give rise to potentially more accurate motifs, capture complex binding sites built upon the basis motif, and eliminate the constraints of the currently employed promoter searching protocols. We also present a measure of motif quality based on the occurrence of the putative motifs in regions observed to contain the binding sites. The assumptions, motif generation, quality assessment and comparison allow the user as much control as their a priori knowledge allows. AVAILABILITY: IGRDB and the datasets mentioned herein are available at http://chipdb.wi.mit.edu/

Amino Acid Motifs↗
PubMed2002

Gene structure identification with MyGV using cDNA evidence and protein homologs to improve ab initio predictions.

UNLABELLED: MyGV is an application to visualize (potentially genome-scale) gene structure annotation and prediction. The output of any external gene prediction program can be easily converted to a generalized format for input into MyGV. The application displays all input simultaneously in graphical representation, with a toggle option for a text-based view. Zooming capabilities allow detailed comparisons for specific genome locations. The tool is particularly helpful for refinement of ab initio predicted gene structures by spliced alignment with cDNA or protein homologs. AVAILABILITY: The program was written in Java and is freely available to non-commercial users by electronic download from http://bioinformatics.iastate.edu/bioinformatics2go/MyGV.

Animals↗
PubMed2003

Predicting HIV drug resistance with neural networks.

MOTIVATION: Drug resistance is a very important factor influencing the failure of current HIV therapies. The ability to predict the drug resistance of HIV protease mutants may be useful in developing more effective and longer lasting treatment regimens. METHODS: The HIV resistance is predicted to two current protease inhibitors, Indinavir and Saquinavir. The problem was approached from two perspectives. First, a predictor was constructed based on the structural features of the HIV protease-drug inhibitor complex. A particular structure was represented by its list of contacts between the inhibitor and the protease. Next, a classifier was constructed based on the sequence data of various drug resistant mutants. In both cases, self-organizing maps were first used to extract the important features and cluster the patterns in an unsupervised manner. This was followed by subsequent labelling based on the known patterns in the training set. RESULTS: The prediction performance of the classifiers was measured by cross-validation. The classifier using the structure information correctly classified previously unseen mutants with an accuracy of between 60 and 70%. Several architectures were tested on the more abundant sequence data. The best single classifier provided an accuracy of 68% and a coverage of 69%. Multiple networks were then combined into various majority voting schemes. The best combination yielded an average of 85% coverage and 78% accuracy on previously unseen data. This is more than two times better than the 33% accuracy expected from a random classifier.

Algorithms↗
PubMed2003

Evaluation of annotation strategies using an entire genome sequence.

MOTIVATION: Genome-wide functional annotation either by manual or automatic means has raised considerable concerns regarding the accuracy of assignments and the reproducibility of methodologies. In addition, a performance evaluation of automated systems that attempt to tackle sequence analyses rapidly and reproducibly is generally missing. In order to quantify the accuracy and reproducibility of function assignments on a genome-wide scale, we have re-annotated the entire genome sequence of Chlamydia trachomatis (serovar D), in a collaborative manner. RESULTS: We have encoded all annotations in a structured format to allow further comparison and data exchange and have used a scale that records the different levels of potential annotation errors according to their propensity to propagate in the database due to transitive function assignments. We conclude that genome annotation may entail a considerable amount of errors, ranging from simple typographical errors to complex sequence analysis problems. The most surprising result of this comparative study is that automatic systems might perform as well as the teams of experts annotating genome sequences.

Amino Acid Sequence↗