The significance is measured by scaling the correlation to the normal by a Fisher transformation and measuring the number of standard deviations from selleck chemical the mean. The tion coefficient and N is the number of genes making up the correlation. The final ranking score is CMAP combined profiles The CMAP contains ranked lists of probes for 6,100 separate perturbagen treatments of four different human cell lines, with the ranking based on response level rela tive to control. The treatments are various multiples of 1,306 different drug like compounds. To generate responder sets that can be used to search SPIED we combined rankings for each separate compound treat ment and converted these into pseudo fold values with associated statistics. The pseudo fold value is defined by gene and min/max are the minimal/maximal ranks.
Remembering that the highest rank corresponds to the most up regulated gene. The SPIED was searched with CMAP profiles corresponding to folds with a p 0. 05 threshold and with at least three replicates. This left 1,218 separate perturbagen probes. We sought to cluster the perturbagens based on predicted target and response profile similarity. The profiles are given in the additional file 1 file. Availability of SPIED The SPIED database and associated executables are available The download consists of the SPIED database together with executables for searching SPIED. Source code files to generate the database and perform query searches are provided together with the executables. Documentation on the database, the execu tables and source code files is also included.
Background During development of the central nervous system a variety of different cell types need to be generated. The three major brain cell types, neurons, astrocytes and oligodendro cytes, arise from neural progenitor cells. Neurons are the first cell type to be generated, starting soon after formation of the neuroectoderm at mid gestation, and astrocytes and oligodendrocytes are born only shortly before birth and continuing into the postnatal period. The mechanisms by which neural stem cells transition from a neuron to an astrocyte generating progenitor are only partially under stood, but secreted growth factors are known to play a role in this process. For example, multiple bone morphogenetic proteins, members of the TGF beta super family, and their receptors are abundantly expressed in the devel oping brain, starting as early as 8.
75 days post coitum. In vitro, BMPs were shown to promote the generation of astrocytes, and in vivo, shown to promote astrocyte formation at the expense of oligodendrocytes. Dacomitinib In particular, BMP2/4 are known to enhance astro gliogenesis and to inhibit neurogenesis through induction of the inhibitory basic helix loop helix transcription factor genes Id1, Id3, and Hes5 which antagonize the proneural gene Ngn1. However, BMP2/4 has also been shown to promote neuronal differentiation in the cortex.