PG is obtained by combining PNDE and PPERT by Fisher's method where PPERT and PNDE are the over-representation of DEGs in a given pathway, and abnormal perturbation of that pathway, respectively.
For a systematic pathway analysis allowing for signaling pathway topology, we conducted a Signaling Pathway Impact Analysis (SPIA) in which a pathway is randomly bootstrapped 3,000 times to calculate two statistical values, namely PNDE and PPERT, which represent the over‐representation of the input genes in a pathway and the abnormal perturbation of a specific pathway, respectively.
These effects may directly or indirectly involve the genetic material and result in developmental perturbations, abnormal embryogenesis and malformations.
For instance, knockdown of spastin (SPG4) caused dramatic defects in spinal motor axon outgrowth, abnormal motility and perturbation of axonal microtubule dynamics (Wood et al., 2006; Butler et al., 2010; Wood et al., 2006).
The idea that abnormal alteration (disruption or enhancement) of specific protein interactions can lead to human diseases complements canonical gene loss/perturbation models and provides new clues on mechanisms underlying human diseases [ 67].
In considering this estimate, one hypothesis is that exceptionally elevated VT swarm activity is evidence of magma intrusion rather than abnormal non-magmatic hydrothermal perturbation.
The membrane organizer of early endosomes, Rab5, is present on synaptic vesicles (Fischer von Mollard et al, 1994), and its perturbation causes abnormal organelles to be present in axons (De Hoop et al, 1994).
The most common features of Mn deficiency in animals were skeletal malformation, and deprivation of Mn intake results in abnormal glucose tolerance and perturbation of lipid and carbohydrate metabolism [ 24- 28].
The mutation results in abnormal neuronal migration in vivo; perturbations in layers II/III and IV of the visual, auditory, and somatosensory cortices; and a fractured pyramidal cell layer in the hippocampus.
