MOTIVATION: The rapid development of high-throughput sequencing technologies has enabled epigeneticists to quantify DNA methylation on a massive scale. Progressive increase in sequencing capacity present challenges in terms of processing analysis and the interpretation of the large amount of data; investigating differential methylation between genome-scale data from multiple samples highlights this challenge. RESULTS: We have developed a differential methylation analysis package (DMAP) to generate coverage-filtered reference methylomes and to identify differentially methylated regions across multiple samples from reduced representation bisulphite sequencing and whole genome bisulphite sequencing experiments. We introduce a novel fragment-based approach for investigating DNA methylation patterns for reduced representation bisulphite sequencing data. Further, DMAP provides the identity of gene and CpG features and distances to the differentially methylated regions in a format that is easily analyzed with limited bioinformatics knowledge. AVAILABILITY AND IMPLEMENTATION: The software has been implemented in C and has been written to ensure portability between different platforms. The source code and documentation is freely available (DMAP: as compressed TAR archive folder) from http://biochem.otago.ac.nz/research/databases-software/. Two test datasets are also available for download from the Web site. Test dataset 1 contains reads from chromosome 1 of a patient and a control, which is used for comparative analysis in the current article. Test dataset 2 contains reads from a part of chromosome 21 of three disease and three control samples for testing the operation of DMAP, especially for the analysis of variance. Example commands for the analyses are included.

A program is described for sequence data entry which allows flexible program control by responding to both the keyboard and a sonic digitizer concurrently. Simplification of the initialization stage of each gel reading has been achieved, in comparison with other programs.

The alignment of homologous sequences with each other and their display has proved a difficult task, despite a frequent requirement for this process. HOMED enables related sequences to be edited and listed in parallel with each other. The editor function uses a full screen editor which emulates the text editors KED and EDT (on PDP-11 and VAX-11 respectively) and which can be adapted to emulate other text editors. This emulation has been adopted to simplify user learning of editing functions. HOMED provides functions for listing the sequences in a variety of formats and for generating a consensus sequence as well as providing a series of tools for maintenance of the sequence database. HOMED has been implemented in Pascal in a modular fashion to enhance portability.

Large DNA sequences are now routinely sequenced by the cloning of randomly generated fragments into single-stranded DNA phage vectors (the 'shotgun' method). Various programs exist for computerized assembly of such fragments, including the phases of data entry, homology searching and gel-management/editing. Many gel-management editors are rudimentary in nature, using either line-editing techniques or using unnatural displays or command systems. Others are available only on restricted types of computer system. The program VTUTIN makes full screen editing along the lines of modern text editors available for the complex data type of sets of sequence gels and their consensus. Not only are the data displayed on the VDU screen in a natural manner, but VTUTIN has also been written to model the command system of a well-established text editor (PDP-11 KED or VAX/VMS EDT) to simplify editor use and learning. VTUTIN has been written in Pascal in a modular form so that wide-spread portability is facilitated. VTUTIN is currently implemented to work on VT-100 type terminals although the modularity of the code should allow straightforward conversion for other terminal types and should also permit simple alteration to model any other text editor.