Abstract:For the analysis of microarray data, clustering techniques are frequently used. Most of such methods are based on hard clustering of data wherein one gene (or sample) is assigned to exactly one cluster. Hard clustering, however, suffers from several drawbacks such as sensitivity to noise and information loss. In contrast, soft clustering methods can assign a gene to several clusters. They can overcome shortcomings of conventional hard clustering techniques and offer further advantages. Thus, we constructed an R package termed Mfuzz implementing soft clustering tools for microarray data analysis. The additional package Mfuzzgui provides a convenient TclTk based graphical user interface.

Altered abundance of several intrinsically unstructured proteins (IUPs) has been associated with perturbed cellular signalling that may lead to pathological conditions such as cancer. Therefore, it is important to understand how cells precisely regulate availability of IUPs. We observe that regulation of transcript clearance, proteolytic degradation, and translational rate contribute to control the abundance of IUPs, some of which are present in low amounts and for short periods of time. Abundant phosphorylation and low stochasticity in transcription and translation indicates that availability of IUPs can be finely tuned. Fidelity in signalling may require that most IUPs are available in appropriate amounts and not present longer than needed.Up to one-third of all eukaryotic proteins have large segments that are unstructured and are commonly referred as intrinsically unstructured proteins (IUPs). These proteins lack a unique structure, either entirely or in parts, when alone in solution (1). The lack of structure is thought to provide several advantages such as (i) increased interaction surface area, (ii) conformational flexibility to interact with several targets, (iii) presence of molecular recognition elements that fold upon binding, (iv) accessible post-translational modification sites and (v) availability of short linear interaction motifs (2-5). These and other properties are ideal for proteins that mediate signaling and coordinate regulatory events and indeed proteins that participate in regulatory and signaling functions are enriched in unstructured segments (6-8) (SOM text S1). Because of their unusual structural and important functional properties, the presence of IUPs in a cell may need to be carefully monitored. In fact, altered abundance of IUPs is associated with several disease conditions. For instance, overexpression of TC-1 (9) or under-expression of Arf (10) and p27 (11) has been linked with various types of cancer. Similarly, over-expression of α-synuclein and tau increases the risk of aggregate formation and has been linked to Parkinson's disease and Alzheimer's disease (12, 13). We therefore tested whether specific control mechanisms affect the availability of IUPs (that is their abundance and residence time) within a cell.Using the Disopred2 software (6), which reports unstructured residues based on the protein sequence, we computed the fraction of the polypeptide that is predicted to be unstructured for every protein in Saccharomyces cerevisiae (14). This allowed us to categorize 1971 sequences as highly structured (S: 0 to 10% of the total length is unstructured), 2711 sequences as moderately unstructured (M: 10 to 30% of the protein is unstructured) and 2020 sequences as highly unstructured (U: 30 to 100% of the protein is unstructured) (Fig. 1). This information was integrated with different genome-scale datasets describing most of the regulatory steps that influence protein synthesis or degradation (table S1, fig. S1) and the * To whom correspondence should be addressed. Email...