Automation for Genomics, Part Two: Sequencers, Microarrays, and Future Trends

Abstract

Automation for genomics has enabled a 43-fold increase in the total finished human genomic sequence in the world in the past four years. This is the second half of a two-part, noncomprehensive review that presents an overview of different types of automation equipment used in genome sequencing. The first part of the review, published in the previous issue, focused on automated procedures used to prepare DNA for sequencing or analysis. This second part of the review presents a look at available DNA sequencers and array technology and concludes with a look at future technologies. Alternate sequencing technologies including mass spectrometry, biochips, and single molecule analysis are included in this review.Sequencing data, essential for many of the medical breakthroughs of today and tomorrow, is currently accumulating at an exponential rate, largely because of advances in sequencing methods and laboratory automation. Instruments are available that can automate nearly every step in the large-scale sequencing process.The first article in this two-part review (Meldrum 2000) presented a description of automation designed for isolating DNA, cloning or amplifying DNA, preparing enzymatic sequencing reactions, and purifying DNA. Part one of the review also showed that the majority of genome centers use both in-house automation and commercial automation (Collins et al. 1998;Wendl et al. 1998;Mullikin and McMurragy 1999;Spurr et al. 1999; see http://www.genome.org for a supplementary table providing a snapshot view of automation used at a number of different genome centers).In this, the second part of the review, the focus is on automation after DNA preparation and sequencing reactions-on obtaining the sequence and its analysis. A discussion of future technologies for DNA sequencing projects is also included. (See the web sites referenced for photos or further details on the instruments presented.)

Dynamics of gene silencing by RNA interference

“…Genome sequencing projects have catalyzed the development of high-throughput technologies (Meldrum, 2000;Collins et al, 2003;Galas and McCormack, 2003) that help identify an increasing number of genetic targets implicated in disease and other important biotechnological applications. This capability has not been matched by equally efficient methods to characterize these genes.…”

Genomics of food-borne bacterial pathogens

“…These two main approaches are now in common use but this field continues to move rapidly and new technical approaches are constantly appearing in the literature (Lipshutz et al 1999;Singh-Gasson et al 1999;Brenner et al 2000;Okamoto et al 2000;Steemers et al 2000;Taton et al 2000;Westin et al 2000;Blohm & Guiseppi-Elie, 2001). Information on general and technical aspects of microarraying is also available from recent reviews (Cheung et al 1999;Graves, 1999;Lipshutz et al 1999;Niemeyer & Blohm, 1999;DeRisi, 2000;Lee et al 2000;Meldrum, 2000;Schuchhardt et al 2000).…”

A Scalable High-Throughput Chemical Synthesizer

“…This need is dramatically illustrated by the large and growing demand for singlestranded DNA or oligonucleotides (often simply referred to as "oligos") (Williams et al 1988;Niece et al 1991;Ivanetich et al 1993;Pon et al 1994;Hager et al 1999;Goforth 2002). Oligos are used as primers in the polymerase chain reaction (PCR) technique (Meldrum 2000a), for the de novo chemical synthesis of genes (Kenneth et al 1988;Dietrich et al 1998), and for spotted DNA microarrays (Meldrum 2000b). Their use has risen significantly over the last decade (Jaklevic et al 1999) and is expected to increase even more, driven largely by the genome sequencing of a number of organisms.…”