In fact, piRNAs consist of more than 30,000 different species, in contrast to only several hundred species of miRNAs. Most piRNAs map to the genome in clusters of 20 to 90 kbs in a strand-specific manner, with each cluster likely representing a long single-stranded RNA precursor, or more often, two non-overlapping and divergently transcribed precursors. Inflammatory Bowel Disease, Crohn��s disease and ulcerative colitis, are multifactorial, complex, lifelong diseases with a broad spectrum of manifestations. The pathophysiology of IBD is still unclear but it is well acknowledged that multiple factors, including genetic, environmental and immunological, contribute to the occurrence and perpetuation of the disease. Furthermore, the patients on occasion also present with extraintestinal manifestations, such as cholangitis, uveitis, peri-anal and oral lesions. The disease severity is quantified by grading symptoms, which are then compiled in a univariate fashion to generate disease activity scores, such as the Crohn��s disease activity index. Evaluating the Granisetron hydrochloride outcome of new drugs in a clinical study is traditionally performed by statistical univariate methods created to discover statistically significant improvements for the treated patient group, in an unbiased way. However, univariate methods need high object inclusion numbers to meet their significance dependency and, in addition, some correlations are of truly multivariate nature. In terms of complex diseases such as IBD, there is also a risk of overseeing clinically meaningful treatment effects. Such treatment effects may be diluted and masked by unrelated phenomena that are involved in the score, but not in the targeted pathophysiology. On one hand, these approaches are obviously required for drug development, both from ethical and business aspects and the regulatory authorities delineate stringent guidelines, which the industry follows for good reasons. The above perspective relates Begacestat mainly to the later development phase, i.e. clinical phase III studies, Research and early development studies, on the other hand, could benefit from parallel approaches, frontloading biological or physiological relevance versus statistical significance. Several studies have indicated that multivariate analyses provide more in depth knowledge than significance test statistics on the physiology and at the systems biology level, and could therefore be applied to the study designs. Such holistic methods can for instance describe how individual animals alter their physiological pattern when they develop disease or when they are subjected to pharmacological treatment. In terms of preclinical models for IBD, more than fifty models have been described including genetically modified, chemically induced, adoptive transfer of T cells and also few spontaneous models. It should be noted that none of these models fully represent any form of human IBD. Rather, they can be viewed upon as mechanistic models illustrating different physiological and pathophysiological mechanisms occurring in the gastrointestinal tract. As such, the models have contributed greatly to our current understanding of the underlying mechanisms of gastrointestinal inflammation and disease pathogenesis. However, the complexity of gastrointestinal inflammation is seldom illustrated in these studies. Rather, there is a bias towards symptom scoring that are compiled into univariate composite indices. Similar to the human situation, these composite disease activity indices may not be informative for the severity of the local inflammation, and may therefore not be optimal endpoints for understanding the underlying mechanisms behind the disease.