Biomedical subjects

Rogier Donders

Publications and source records attributed to Rogier Donders.

3 recordsLinked to original sources

PubMed2004

Predicting gene function through systematic analysis and quality assessment of high-throughput data.

MOTIVATION: Determining gene function is an important challenge arising from the availability of whole genome sequences. Until recently, approaches based on sequence homology were the only high-throughput method for predicting gene function. Use of high-throughput generated experimental data sets for determining gene function has been limited for several reasons. RESULTS: Here a new approach is presented for integration of high-throughput data sets, leading to prediction of function based on relationships supported by multiple types and sources of data. This is achieved with a database containing 125 different high-throughput data sets describing phenotypes, cellular localizations, protein interactions and mRNA expression levels from Saccharomyces cerevisiae, using a bit-vector representation and information content-based ranking. The approach takes characteristic and qualitative differences between the data sets into account, is highly flexible, efficient and scalable. Database queries result in predictions for 543 uncharacterized genes, based on multiple functional relationships each supported by at least three types of experimental data. Some of these are experimentally verified, further demonstrating their reliability. The results also generate insights into the relative merits of different data types and provide a coherent framework for functional genomic datamining. AVAILABILITY: Free availability over the Internet. CONTACT: f.c.p.holstege@med.uu.nl SUPPLEMENTARY INFORMATION: http://www.genomics.med.uu.nl/pub/pk/comb_gen_network.

Computer Simulation↗

PubMed2003

Hearing loss at school age in survivors of bacterial meningitis: assessment, incidence, and prediction.

OBJECTIVES: To establish the incidence of sensorineural hearing loss in children who survived non-Haemophilus influenzae type B (Hib) bacterial meningitis, to highlight the actual percentage whose hearing was evaluated, and to develop a prediction rule to identify those who are at risk of hearing loss. METHODS: In 1999, we compiled a cohort of 628 school-aged children who were born between January 1986 and December 1994 and had survived non-Hib bacterial meningitis between January 1990 and December 1995. Presence of sensorineural hearing loss (>25 dB) was determined, based on information from questionnaires and medical records. Potential risk factors for hearing loss were obtained from medical records; independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. RESULTS: The incidence of hearing loss was 7%. The hearing of 68% of the children was evaluated as part of their routine follow-up after bacterial meningitis, resulting in the detection of 75% of the cases of hearing loss. The remaining 25% were detected after this follow-up had ended. Using a prediction rule based on 5 factors-duration of symptoms before admission >2 days, absence of petechiae, cerebrospinal fluid glucose level <or=0.6 mmol/L, Streptococcus pneumoniae, and ataxia-62% of the postmeningitic children were selected as being at risk. All cases of hearing loss were in this at-risk group. CONCLUSIONS: Hearing loss can be predicted satisfactorily. When the hearing of children who are predicted to be at risk is tested as part of their routine follow-up, no children with hearing loss need be missed.

Adolescent↗

PubMed2002

Protein interaction verification and functional annotation by integrated analysis of genome-scale data.

Assays capable of determining the properties of thousands of genes in parallel present challenges with regard to accurate data processing and functional annotation. Collections of microarray expression data are applied here to assess the quality of different high-throughput protein interaction data sets. Significant differences are found. Confidence in 973 out of 5342 putative two-hybrid interactions from S. cerevisiae is increased. Besides verification, integration of expression and interaction data is employed to provide functional annotation for over 300 previously uncharacterized genes. The robustness of these approaches is demonstrated by experiments that test the in silico predictions made. This study shows how integration improves the utility of different types of functional genomic data and how well this contributes to functional annotation.

Animals↗