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. 2015 Nov 8;44(5):2093–2109. doi: 10.1093/nar/gkv1210

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© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Figure 4. — (A) Median length of mRNA and pre-mRNA transcripts expressed on the microarray as a function of the modulation: ‘Down’ represents the number of transcripts down-regulated 24 h post treatment (240) negatively correlated to ALT increase at 96 h, ‘Up’ represents the number of transcripts up-regulated 24 h post treatment (353) positively correlated to ALT increase at 96 h (Prob > 0.000001, r² > 0.54). Distribution of mRNA (B) and pre-mRNA (C) transcripts expressed on array. The blue horizontal line represents the median length of down-regulated transcripts, in gray unchanged transcripts and in red, up-regulated transcripts. (D) Cumulative probability plot of the basal expression levels of long (pre-mRNA length > 125 000 b) down-regulated transcripts with high (red), medium (green) or minimal correlation to ALT increase, shows transcripts with low level of basal expression tend to exhibit a low level of correlation with ALT increase following treatment with hepatotoxic ASOs. (E–G) Cumulative probability plot of fold change of modulated transcripts binned by pre-mRNA length for three hepatotoxic LNA ASOs (FXI-1, SOD1–2 and FVII-3 LNA at 33 mg/kg, respectively) treatment group are represented. The proportion of transcripts as well as the intensity of transcript down-regulation increases as a function of the length of pre-mRNA transcripts.