GeoChip covers a wide range of functional genes and currently includes sequences from bacteria, Achaea, fungi, and viruses. The first step in designing new probes for the array is deciding which processes should be included. Then genes for enzymes or proteins that are key to the process of interest are selected. These could be catalytic subunits or proteins with recognition sites or that provide functional specificity. Next, keywords are selected to search public sequence databases (e.g., GenBank). The keywords should be as broad as possible since proteins from different microorganisms may be annotated differently or have more general or specific annotations. Once the sequences are downloaded, they are confirmed by HMMER alignment 1 with preselected seed sequences. The seed sequences are those sequences for which the protein identity and function have been experimentally confirmed. This is a critical step in the design process and these sequences should be selected with care. The HMMER confirmed sequences are then used to design gene-or group-specific 50-mer oligonucleotide probes using new versions of the CommOligo software (Li et al., 2005) and experimentally determined criteria based on sequence homology (≤90% identity for gene-specific probes, and ≥96% for group-specific probes), continuous stretch length (≤20 bases for gene-specific probes, and ≥35 for group-specific probes), and free energy (≥35 kJ mol −1 for gene-specific probes, and ≤60 kJ mol −1 for group-specific probes; He et al., 2005b; Liebich et al., 2006) . The probes are then BLASTed against the GenBank database to confirm specificity. Keywords, downloaded sequences, seed sequences, HMMER confirmed sequences, and designed probes are stored in corresponding databases for use in future array updates.