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The article reflects on genomic analysis of single cells. Topics include a map of the Drosophila genome published by researcher Calvin Bridges in 1935, the polymerase chain reaction, and biochemical amplification technologies to single cells and single-cell sequencing. Other topics include development in human genome analysis, an example of sequence variation in human leukocyte antigen (HLA) and the preimplantation genetic diagnosis (PGD) of couples conceiving through in vitro fertilization.

We report a single-molecule assay for nucleic-acid enzymes on flow-stretched DNA templates. To facilitate the detection of slow or intermittent enzymatic activities, we developed the assay with 15-nm spatial resolution at a frame rate of 1 Hz and ∼10 nm mechanical stability over the timescale of hours. With multiplexed data collection, we applied the assay to φ29 DNA polymerase, HIV-1 reverse transcriptase, λ exonuclease and Escherichia coli RNA polymerase. [ABSTRACT FROM AUTHOR]

The bootstrap can be used to assess uncertainty of sample estimates. [ABSTRACT FROM AUTHOR]

The article discusses the use of a nested analysis of variance approach for studies with hierarchical noise sources. According to the authors, people can use the relative noise contribution of each layer to optimally allocate experimental resources using nested analysis of variance (ANOVA), which addresses replication and blocking. The authors mention the impact of fixed and random factors in the presence of experimental error.

The article discusses research on types of replication in multilevel experimental designs which can be used to limit the effect of spurious variation on hypothesis testing and parameter estimation. Topics discussed include genome sequencing, measurement of the expression of a specific gene in liver cells in mice, the practical effect of the number of replicates on inference errors in analysis of differences of means or variances, and preference for biological over technical replicates.