Biomedical subjects

Maurizio Pellegrino

Publications and source records attributed to Maurizio Pellegrino.

3 recordsLinked to original sources

PubMed2006

Microarray and large-scale in silico--based identification of genes functionally related to Haptoglobin and/or Hemopexin.

Haptoglobin and Hemopexin are plasma acute phase proteins that bind with high-affinity hemoglobin and heme, respectively. They play a key role in the protection against oxidative stress and inflammation. To dissect in more detail the mechanism of action of Haptoglobin and Hemopexin, it is important to identify their downstream effectors as well as genes functionally related to them. To this end, we performed a cDNA microarray analysis to compare gene expression profiles of the liver of Haptoglobin and Hemopexin single and double null mice to that of wild-type controls. Then, to extract the best candidates considered to be functionally related to Haptoglobin and/or Hemopexin from microarray-derived gene lists, we used a bioinformatic approach consisting in the screening of published microarray data for genes showing coexpression with Haptoglobin or Hemopexin. This strategy allowed us to identify a group of genes coexpressed with Haptoglobin or Hemopexin and transcriptionally modulated by their lack. These genes present a high probability to be functionally related to Haptoglobin and Hemopexin. Based on literature data, we picked up from this group of genes the ras suppressor Rsu1, the member of the G-protein signal transduction family Gnai2, and the cytokine Mdk as the best candidates mediating the anti-inflammatory action of Haptoglobin and Hemopexin.

Animals↗

PubMed2005

Harshlight: a "corrective make-up" program for microarray chips.

BACKGROUND: Microscopists are familiar with many blemishes that fluorescence images can have due to dust and debris, glass flaws, uneven distribution of fluids or surface coatings, etc. Microarray scans do show similar artifacts, which might affect subsequent analysis. Although all but the starkest blemishes are hard to find by the unaided eye, particularly in high-density oligonucleotide arrays (HDONAs), few tools are available to help with the detection of those defects. RESULTS: We develop a novel tool, Harshlight, for the automatic detection and masking of blemishes in HDONA microarray chips. Harshlight uses a combination of statistic and image processing methods to identify three different types of defects: localized blemishes affecting a few probes, diffuse defects affecting larger areas, and extended defects which may invalidate an entire chip. CONCLUSION: We demonstrate the use of Harshlight can materially improve analysis of HDONA chips, especially for experiments with subtle changes between samples. For the widely used MAS5 algorithm, we show that compact blemishes cause an average of 8 gene expression values per chip to change by more than 50%, two of them by more than twofold; our masking algorithm restores about two thirds of this damage. Large-scale artifacts are successfully detected and eliminated.

Algorithms↗

PubMed2004

CLOE: identification of putative functional relationships among genes by comparison of expression profiles between two species.

BACKGROUND: Public repositories of microarray data contain an incredible amount of information that is potentially relevant to explore functional relationships among genes by meta-analysis of expression profiles. However, the widespread use of this resource by the scientific community is at the moment limited by the limited availability of effective tools of analysis. We here describe CLOE, a simple cDNA microarray data mining strategy based on meta-analysis of datasets from pairs of species. The method consists in ranking EST probes in the datasets of the two species according to the similarity of their expression profiles with that of two EST probes from orthologous genes, and extracting orthologous EST pairs from a given top interval of the ranked lists. The Gene Ontology annotation of the obtained candidate partners is then analyzed for keywords overrepresentation. RESULTS: We demonstrate the capabilities of the approach by testing its predictive power on three proteomically-defined mammalian protein complexes, in comparison with single and multiple species meta-analysis approaches. Our results show that CLOE can find candidate partners for a greater number of genes, if compared to multiple species co-expression analysis, but retains a comparable specificity even when applied to species as close as mouse and human. On the other hand, it is much more specific than single organisms co-expression analysis, strongly reducing the number of potential candidate partners for a given gene of interest. CONCLUSIONS: CLOE represents a simple and effective data mining approach that can be easily used for meta-analysis of cDNA microarray experiments characterized by very heterogeneous coverage. Importantly, it produces for genes of interest an average number of high confidence putative partners that is in the range of standard experimental validation techniques.

Animals↗