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Biomedical subjects

A Califano

Publications and source records attributed to A Califano.

At least 19 recordsLinked to original sources
PubMed2001

Advances in sequence analysis.

In its early days, the entire field of computational biology revolved almost entirely around biological sequence analysis. Over the past few years, however, a number of new non-sequence-based areas of investigation have become mainstream, from the analysis of gene expression data from microarrays, to whole-genome association discovery, and to the reverse engineering of gene regulatory pathways. Nonetheless, with the completion of private and public efforts to map the human genome, as well as those of other organisms, sequence data continue to be a veritable mother lode of valuable biological information that can be mined in a variety of contexts. Furthermore, the integration of sequence data with a variety of alternative information is providing valuable and fundamentally new insight into biological processes, as well as an array of new computational methodologies for the analysis of biological data.

Computational Biology↗
PubMed2000

Systematic and fully automated identification of protein sequence patterns.

We present an efficient algorithm to systematically and automatically identify patterns in protein sequence families. The procedure is based on the Splash deterministic pattern discovery algorithm and on a framework to assess the statistical significance of patterns. We demonstrate its application to the fully automated discovery of patterns in 974 PROSITE families (the complete subset of PROSITE families which are defined by patterns and contain DR records). Splash generates patterns with better specificity and undiminished sensitivity, or vice versa, in 28% of the families; identical statistics were obtained in 48% of the families, worse statistics in 15%, and mixed behavior in the remaining 9%. In about 75% of the cases, Splash patterns identify sequence sites that overlap more than 50% with the corresponding PROSITE pattern. The procedure is sufficiently rapid to enable its use for daily curation of existing motif and profile databases. Third, our results show that the statistical significance of discovered patterns correlates well with their biological significance. The trypsin subfamily of serine proteases is used to illustrate this method's ability to exhaustively discover all motifs in a family that are statistically and biologically significant. Finally, we discuss applications of sequence patterns to multiple sequence alignment and the training of more sensitive score-based motif models, akin to the procedure used by PSI-BLAST. All results are available at httpl//www.research.ibm.com/spat/.

Algorithms↗
PubMed2000

SPLASH: structural pattern localization analysis by sequential histograms.

MOTIVATION: The discovery of sparse amino acid patterns that match repeatedly in a set of protein sequences is an important problem in computational biology. Statistically significant patterns, that is patterns that occur more frequently than expected, may identify regions that have been preserved by evolution and which may therefore play a key functional or structural role. Sparseness can be important because a handful of non-contiguous residues may play a key role, while others, in between, may be changed without significant loss of function or structure. Similar arguments may be applied to conserved DNA patterns. Available sparse pattern discovery algorithms are either inefficient or impose limitations on the type of patterns that can be discovered. RESULTS: This paper introduces a deterministic pattern discovery algorithm, called Splash, which can find sparse amino or nucleic acid patterns matching identically or similarly in a set of protein or DNA sequences. Sparse patterns of any length, up to the size of the input sequence, can be discovered without significant loss in performances. Splash is extremely efficient and embarrassingly parallel by nature. Large databases, such as a complete genome or the non-redundant SWISS-PROT database can be processed in a few hours on a typical workstation. Alternatively, a protein family or superfamily, with low overall homology, can be analyzed to discover common functional or structural signatures. Some examples of biologically interesting motifs discovered by Splash are reported for the histone I and for the G-Protein Coupled Receptor families. Due to its efficiency, Splash can be used to systematically and exhaustively identify conserved regions in protein family sets. These can then be used to build accurate and sensitive PSSM or HMM models for sequence analysis. AVAILABILITY: Splash is available to non-commercial research centers upon request, conditional on the signing of a test field agreement. CONTACT: acal@us.ibm.com, Splash main page http://www.research.ibm.com/splash

Algorithms↗
PubMed2000

Analysis of gene expression microarrays for phenotype classification.

Several microarray technologies that monitor the level of expression of a large number of genes have recently emerged. Given DNA-microarray data for a set of cells characterized by a given phenotype and for a set of control cells, an important problem is to identify "patterns" of gene expression that can be used to predict cell phenotype. The potential number of such patterns is exponential in the number of genes. In this paper, we propose a solution to this problem based on a supervised learning algorithm, which differs substantially from previous schemes. It couples a complex, non-linear similarity metric, which maximizes the probability of discovering discriminative gene expression patterns, and a pattern discovery algorithm called SPLASH. The latter discovers efficiently and deterministically all statistically significant gene expression patterns in the phenotype set. Statistical significance is evaluated based on the probability of a pattern to occur by chance in the control set. Finally, a greedy set covering algorithm is used to select an optimal subset of statistically significant patterns, which form the basis for a standard likelihood ratio classification scheme. We analyze data from 60 human cancer cell lines using this method, and compare our results with those of other supervised learning schemes. Different phenotypes are studied. These include cancer morphologies (such as melanoma), molecular targets (such as mutations in the p53 gene), and therapeutic targets related to the sensitivity to an anticancer compounds. We also analyze a synthetic data set that shows that this technique is especially well suited for the analysis of sub-phenotype mixtures. For complex phenotypes, such as p53, our method produces an encouragingly low rate of false positives and false negatives and seems to outperform the others. Similar low rates are reported when predicting the efficacy of experimental anticancer compounds. This counts among the first reported studies where drug efficacy has been successfully predicted from large-scale expression data analysis.

Algorithms↗
PubMed1999

Clinical trial of the efficacy and safety of oral etretinate with calcipotriol cream compared with etretinate alone in moderate-severe psoriasis.

BACKGROUND: The aim of this clinical trial was to assess the efficacy and safety of calcipotriol cream associated with oral etretinate compared with etretinate alone in the treatment of moderate-severe psoriasis. METHODS: This controlled multicenter trial, within patients (hemiparts), enrolled 86 in- or out-patients (62 males, 24 females), mean (+/-SD) age 57.1 +/- 14.2 years, with psoriasis vulgaris on both sides of the body, and mean (+/-SE) baseline PASI score (Psoriasis Area and Severity Index) 30.7 +/- 0.9. All patients took oral etretinate 50 mg/day and applied calcipotriol cream (50 microg/g) on one half of their body twice a day. Treatment was continued for 9 weeks, and patients were seen every 3 weeks. RESULTS: At the end of the first 3 weeks the PASI score indicated a significant clinical difference between the two sides of the body (P < 0.001, ANOVA), with a reduction of 50.7% in the score for the calcipotriol-treated half, compared with a 39% reduction for the untreated half. By the 9th week of treatment the PASI score was 81.4% lower on the treated half, and 70.3% on the untreated side (P < 0.001, ANOVA). CONCLUSIONS: These findings suggest that patients with moderate-severe psoriasis might benefit from treatment with etretinate plus calcipotriol, with the aim of achieving a faster response and an overall smaller total dose of etretinate.

Administration, Oral↗
PubMed1998

Diaper dermatitis in an adult. A case of erythema papuloerosive of Sevestre and Jacquet.

BACKGROUND: Irritants, friction and occlusion favor dermatitis or inflammatory reactions in the diaper area. Diaper dermatitis is not found exclusively in children but also in adults wearing a diaper for urinary incontinence. CASE: We report a case of eroded papules on the labia majora in a woman with urinary incontinence. CONCLUSION: Erythema papuloerosive of Sevestre and Jacquet is an unusual dermatitis due to irritant agents in the diaper area that may also affect adults. As this dermatitis may resemble neoplasia and venereal disease, it can be easily misdiagnosed, especially in adults.

Aged↗
PubMed1995

Open study of topical 0.025% tretinoin in the treatment of vulvar lichen sclerosus. One year of therapy.

OBJECTIVE: To study the use of topical tretinoin for treating vulvar lichen sclerosus. STUDY DESIGN: An open, uncontrolled clinical study on 22 patients affected by histologically confirmed vulvar lichen sclerosus. Topical 0.025% tretinoin was applied once a day, five days a week, for one year. Clinical and histologic parameters were evaluated before and after therapy, and statistical analysis was performed. RESULTS: Symptoms, gross appearance and histopathologic features improved in a highly significant manner (P < .001). Cutaneous side effects were observed but rapidly disappeared, and no patient left the study for this reason. Maintenance of results was observed at the 4-13-month follow-up visits. CONCLUSION: Topical tretinoin seems feasible for use in the topical treatment of vulvar lichen sclerosus.

Administration, Topical↗
PubMed1993

FLASH: a fast look-up algorithm for string homology.

A key issue in managing today's large amounts of genetic data is the availability of efficient, accurate, and selective techniques for detecting homologies (similarities) between newly discovered and already stored sequences. A common characteristic of today's most advanced algorithms, such as FASTA, BLAST, and BLAZE is the need to scan the contents of the entire database, in order to find one or more matches. This design decision results in either excessively long search times or, as is the case of BLAST, in a sharp trade-off between the achieved accuracy and the required amount of computation. The homology detection algorithm presented in this paper, on the other hand, is based on a probabilistic indexing framework. The algorithm requires minimal access to the database in order to determine matches. This minimal requirement is achieved by using the sequences of interest to generate a highly redundant number of very descriptive tuples; these tuples are subsequently used as indices in a table look-up paradigm. In addition to the description of the algorithm, theoretical and experimental results on the sensitivity and accuracy of the suggested approach are provided. The storage and computational requirements are described and the probability of correct matches and false alarms is derived. Sensitivity and accuracy are shown to be close to those of dynamic programming techniques. A prototype system has been implemented using the described ideas. It contains the full Swiss-Prot database rel 25 (10 MR) and the genome of E. Coli (2 MR). The system is currently being expanded to include the complete Genbank database.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1986

Effects of a new pyrazolo [3, 4-d]pyrimidine on growth and morphology of Candida albicans.

A new pyrazolo [3, 4-d]pyrimidine derivative was synthesized and its antifungal activity evaluated in vitro against mycelial and yeast cells of Candida albicans. The most striking ultrastructural changes following treatment with 10-30 micrograms/ml (mycelia) and 25-75 micrograms/ml (yeasts) consisted in the deterioration of the organelle membranes and in aberrant thickenings of the cell wall. The complete disorganization of the cytoplasmic structures seemed to be the final event.

Antifungal Agents↗
PubMed1980

Preliminary results of a clinical trial relative to the use of rifamycin SV in the treatment of herpes zoster.

In a controlled clinical trial undertaken in ten Italian centres, rifamycin SV was compared to associations of various drugs such as erythromycin, aureomycin, multivitamin preparations, etc, in the treatment of herpes zoster. Up to now 144 patients, suffering from herpes zoster at different localizations, were divided into three groups and randomly given either rifamycin SV by intramuscular injection and topically, or rifamycin SV by injection only, or the routine treatment used at the particular centre in question. To evaluate the effectiveness of the treatments, the presence of subjective and objective symptoms was determined before treatment started and daily thereafter. The duration, in days, of the most important symptoms, such as erythema, vesicles, scabs and pain, was considered for this partial evaluation. All the above-mentioned symptoms constantly showed a shorter duration in the two groups treated with rifamycin SV compared to the group treated with other therapies, with differences as significant on statistical calculation as they were important on the level of a clinical evaluation of the disease's course.

Administration, Topical↗