CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.

In recent years improvements to existing programs and the introduction of new iterative algorithms have changed the state-of-the-art in protein sequence alignment. This paper presents the first systematic study of the most commonly used alignment programs using BAliBASE benchmark alignments as test cases. Even below the 'twilight zone' at 10-20% residue identity, the best programs were capable of correctly aligning on average 47% of the residues. We show that iterative algorithms often offer improved alignment accuracy though at the expense of computation time. A notable exception was the effect of introducing a single divergent sequence into a set of closely related sequences, causing the iteration to diverge away from the best alignment. Global alignment programs generally performed better than local methods, except in the presence of large N/C-terminal extensions and internal insertions. In these cases, a local algorithm was more successful in identifying the most conserved motifs. This study enables us to propose appropriate alignment strategies, depending on the nature of a particular set of sequences. The employment of more than one program based on different alignment techniques should significantly improve the quality of automatic protein sequence alignment methods. The results also indicate guidelines for improvement of alignment algorithms.

In a single experiment, chromatin immunoprecipitation combined with high throughput sequencing (ChIP-seq) provides genome-wide information about a given covalent histone modification or transcription factor occupancy. However, time efficient bioinformatics resources for extracting biological meaning out of these gigabyte-scale datasets are often a limiting factor for data interpretation by biologists. We created an integrated portable ChIP-seq data interpretation platform called seqMINER, with optimized performances for efficient handling of multiple genome-wide datasets. seqMINER allows comparison and integration of multiple ChIP-seq datasets and extraction of qualitative as well as quantitative information. seqMINER can handle the biological complexity of most experimental situations and proposes methods to the user for data classification according to the analysed features. In addition, through multiple graphical representations, seqMINER allows visualization and modelling of general as well as specific patterns in a given dataset. To demonstrate the efficiency of seqMINER, we have carried out a comprehensive analysis of genome-wide chromatin modification data in mouse embryonic stem cells to understand the global epigenetic landscape and its change through cellular differentiation.