Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation.

By informing timely targeted treatments, rapid whole-genome sequencing can improve the outcomes of seriously ill children with genetic diseases, particularly infants in neonatal and pediatric intensive care units (ICUs). The need for highly qualified professionals to decipher results, however, precludes widespread implementation. We describe a platform for population-scale, provisional diagnosis of genetic diseases with automated phenotyping and interpretation.

Finding non-coding RNAs through genome-scale clustering.

Non-coding RNAs (ncRNAs) are transcripts that do not code for proteins. Recent findings have shown that RNA-mediated regulatory mechanisms influence a substantial portion of typical microbial genomes. We present an efficient method for finding potential ncRNAs in bacteria by clustering genomic sequences based on homology inferred from both primary sequence and secondary structure.

Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline.

We applied a computational pipeline based on comparative genomics to bacteria, and identified 22 novel candidate RNA motifs. We predicted six to be riboswitches, which are mRNA elements that regulate gene expression on binding a specific metabolite. In separate studies, we confirmed that two of these are novel riboswitches.

Deletion mutations caused by DNA strand slippage in Acinetobacter baylyi.

Short nucleotide sequence repetitions in DNA can provide selective benefits and also can be a source of genetic instability arising from deletions guided by pairing between misaligned strands. These findings raise the question of how the frequency of deletion mutations is influenced by the length of sequence repetitions and by the distance between them. An experimental approach to this question was presented by the heat-sensitive phenotype conferred by pcaG1102, a 30-bp deletion in one of the structural genes for Acinetobacter baylyi protocatechuate 3,4-dioxygenase, which is required for growth with quinate.