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Biomedical subjects

Michael Molla

Publications and source records attributed to Michael Molla.

3 recordsLinked to original sources

Mutation discovery in bacterial genomes: metronidazole resistance in Helicobacter pylori.

We developed a microarray hybridization-based method, 'comparative genome sequencing' (CGS), to find mutations in bacterial genomes and used it to study metronidazole resistance in H. pylori. CGS identified mutations in several genes, most likely affecting metronidazole activation, and produced no false positives in analysis of three megabases. We conclude that CGS identifies mutations in bacterial genomes efficiently, should enrich understanding of systems biology and genome evolution, and help track pathogens during outbreaks.

Anti-Infective Agents↗

A self-tuning method for one-chip SNP identification.

Current methods for interpreting oligonucleotide-based SNP-detection microarrays, SNP chips, are based on statistics and require extensive parameter tuning as well as extremely high-resolution images of the chip being processed. We present a method, based on a simple data-classification technique called nearest-neighbors that, on haploid organisms, produces results comparable to the published results of the leading statistical methods and requires very little in the way of parameter tuning. Furthermore, it can interpret SNP chips using lower-resolution scanners of the type more typically used in current microarray experiments. Along with our algorithm, we present the results of a SNP-detection experiment where, when independently applying this algorithm to six identical SARS SNP chips, we correctly identify all 24 SNPs in a particular strain of the SARS virus, with between 6 and 13 false positives across the six experiments.

Algorithms↗

Gene expression analysis using oligonucleotide arrays produced by maskless photolithography.

Microarrays containing 195,000 in situ synthesized oligonucleotide features have been created using a benchtop, maskless photolithographic instrument. This instrument, the Maskless Array Synthesizer (MAS), uses a digital light processor (DLP) developed by Texas Instruments. The DLP creates the patterns of UV light used in the light-directed synthesis of oligonucleotides. This digital mask eliminates the need for expensive and time-consuming chromium masks. In this report, we describe experiments in which we tested this maskless technology for DNA synthesis on glass surfaces. Parameters examined included deprotection rates, repetitive yields, and oligonucleotide length. Custom gene expression arrays were manufactured and hybridized to Drosophila melanogaster and mouse samples. Quantitative PCR was used to validate the gene expression data from the mouse arrays.

Animals↗