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. 2017 Aug 22;10:266. doi: 10.3389/fnmol.2017.00266

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Copyright © 2017 Pezzini, Bianchi, Benfatto, Griggio, Doccini, Carrozzo, Dapkunas, Delledonne, Santorelli, Lalowski and Simonati.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Bioinformatic survey of identified differentially expressed genes in wild-type and mutated CLN1 cell lines. (A–C) Categorization by Ingenuity Pathway Analysis (IPA, Qiagen) of DEGs in differentiated SH-SY5Y cells. Molecular and Cellular Functions as well as Physiological System Development and Functions IPA classes were examined. Categories of Cellular Development, Cell-to-Cell Signalling and Interaction, Cell Morphology as well as Nervous System Development and Function with lowest B-H corrected p-values were further scrutinized. The number of genes assigned to each category is reported. Statistical significance is reported as –log₁₀ of Benjamini-Hochberg corrected p-value. (D) Heat-map representation depicted most meaningful IPA functional annotations enclosed in Cellular Development, Cell-to-Cell Signalling and Interaction, Cell Morphology and Nervous System Development and Function. Cellular functions correlating with morphological changes of neuronal cells (neuritogenesis, growth/branching/ morphogenesis of neurites and axonogenesis) and neuronal commitment (differentiation of neurons, development of neurons) were commonly affected in SH-p.wtCLN1 and, to a lesser extent, in the two mutated cell lines, following a gradient according to z-scores (from highest to lowest). Functions related to neuronal transmission (long-term potentiation, secretion of neurotransmitter and neurotransmission) were also annotated. Notably, other annotations related to sprouting of neuronal processes (dendritic growth/branching, shape change of neurites, shape change/branching of neurons, guidance of axons) as well as synaptic transmission (developmental process of synapse, long-term potentiation of synapse, plasticity of synapse, release of neurotransmitter and action potential of cells) were selectively assigned to SH-p.wtCLN1 cells only. Functional annotations, shared among the IPA classes are marked by dots. Colored squares represent either a predicted activation (red) or a predicted inhibition (green) according to z-score calculated by IPA algorithm; higher color intensity correlates with more significant bioinformatic prediction.