FACT – a framework for the functional interpretation of high-throughput experiments

BACKGROUND: Interpreting the results of high-throughput experiments, such as those obtained from DNA-microarrays, is an often time-consuming task due to the high number of data-points that need to be analyzed in parallel. It is usually a matter of extensive testing and unknown beforehand, which of the possible approaches for the functional analysis will be the most informative RESULTS: To address this problem, we have developed the Flexible Annotation and Correlation Tool (FACT). FACT allows for detection of important patterns in large data sets by simplifying the integration of heterogeneous data sources and the subsequent application of different algorithms for statistical evaluation or visualization of the annotated data. The system is constantly extended to include additional annotation data and comparison methods. CONCLUSION: FACT serves as a highly flexible framework for the explorative analysis of large genomic and proteomic result sets. The program can be used online; open source code and supplementary information are available at

Identifying an interaction site between MutH and the C-terminal domain of MutL by crosslinking, affinity purification, chemical coding and mass spectrometry

To investigate protein–protein interaction sites in the DNA mismatch repair system we developed a crosslinking/mass spectrometry technique employing a commercially available trifunctional crosslinker with a thiol-specific methanethiosulfonate group, a photoactivatable benzophenone moiety and a biotin affinity tag. The XACM approach combines photocrosslinking (X), in-solution digestion of the crosslinked mixtures, affinity purification via the biotin handle (A), chemical coding of the crosslinked products (C) followed by MALDI-TOF mass spectrometry (M). We illustrate the feasibility of the method using a single-cysteine variant of the homodimeric DNA mismatch repair protein MutL. Moreover, we successfully applied this method to identify the photocrosslink formed between the single-cysteine MutH variant A223C, labeled with the trifunctional crosslinker in the C-terminal helix and its activator protein MutL. The identified crosslinked MutL-peptide maps to a conserved surface patch of the MutL C-terminal dimerization domain. These observations are substantiated by additional mutational and chemical crosslinking studies. Our results shed light on the potential structures of the MutL holoenzyme and the MutH–MutL–DNA complex

The STR polymorphism (AAAAT)n within the intron 1 of the tumor protein 53 (TP53) locus in 17 populations of different ethnic groups of Africa, America, Asia and Europe

artículo arbitrado -- Universidad de Costa Rica, Instituto de investigaciones en Salud. 2004The SIR (A.AAAT). within intron 1 of the TP53 Locus was screened in 17 populations from 3 main ethnic groups: Europeans, Asiatics, and Africans. and from the hybrid population of Costa Rica (1968 samples). Three alleles, 126)7 (bp/copies of the repeat), 13118 and 136/9 were the most prevalent in all populations. Other alleles rarely reached frequencies of 10% or higher. Observed heterozygosities ranged between 0.351 and 0.829. Patterns of diversity fit well with both the geographic origin of the samples and the history of the populations screened. A statistical test suggests that single-step mutational events have been the main mechanism producing new alleles at this locus. Fixation indexes (R57) for this marker showed an effect of population subdivision on divergence only within the Asiatic group; they were insensitive at the level of major ethnic groups as well as within Africans and within EuropeansSe estudio el polimorfismo del microsatelite (AAAAI), del intron 1 del gene TP53 en 17 poblaciones de 3 grupos etnicos: europeos, asiaticos, y africanos subsaharianos, asi coma de la poblacion hibrida de Costa Rica (en total 1968 muestras). Tres aides, 12617 (pares de bases/ copias de la repetición), 131/8 y 136/9 fueron los mas frecuentes en todas las poblaciones, aunque se observaron otros alelos usualmente a frecuencias menores al 10%. Las heterocigosis observadas variaron de 0.351 a 0.829. La distribucion de la universidad parece concordar con el origen geográfico de las muestras y con la historia de las poblaciones estudiadas. Una prueba estadística indica que el evento mutacional que mas alelos nuevos produce en ese marcador es el de un solo paso (expansión o contracción de una cola copia de la repeticion). El indice de fijacion R„ mostro los efectos de la subdivision de poblaciones solo dentro del grupo de los asiaticos y mostro falta de sensibilidad cuando los grupos comparados eran de nivetes superiores de clasificacion (europeos, asiaticos, y africanos) o cuando la comparación se hizo entre los grupos mas antiguos (africanos y europeos).Universidad de costa Rica, Instituto de investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA