Table 5.

Enriched toxicity functions elucidated by the differentially regulated miRs associated with the necrotic liver disease category, the K18 M30 and/or M65 hepatocyte death biomarkers, or PCB exposures.

Enriched tissue specific toxicity	$p$-Value	Associated miRs
Categorical liver disease-associated miRs
Renal tissue
Glomerular injury	$1.34\times {10}^{-07}$	let-7d-5p, miR-99a-5p, miR-197-3p, miR-320a
Renal inflammation	$1.34\times {10}^{-07}$	let-7d-5p, miR-99a-5p, miR-197-3p, miR-320a
Renal nephritis	$1.34\times {10}^{-07}$	let-7d-5p, miR-99a-5p, miR-197-3p, miR-320a
Liver tissue
Hepatocellular carcinoma	$3.02\times {10}^{-06}$–$1.1\times {10}^{-02}$	let-7d-5p, miR-99a-5p, miR-122-5p, miR-17-5p, miR-192-5p, miR-221-3p
Liver hyperplasia/hyperproliferation	$3.02\times {10}^{-06}$–$1.1\times {10}^{-02}$	let-7d-5p, miR-99a-5p, miR-122-5p, miR-17-5p, miR-192-5p, miR-221-3p
Liver inflammation/hepatitis	$2.75\times {10}^{-04}$	miR-99a-5p, miR-221-3p
Liver cirrhosis	$4.74\times {10}^{-03}$	miR-99a-5p, miR-221-3p
Cardiac tissue
Cardiac dilation	$7.36\times {10}^{-03}$	let-7d-5p, miR-17-5p
Cardiac enlargement	$7.36\times {10}^{-03}$	let-7d-5p, miR-17-5p
Hepatocyte death biomarker-associated miRs
Renal tissue
Glomerular injury	$1.23\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15b-5p, miR-197-3p, miR-30c-5p, miR-486-5p
Renal inflammation	$1.23\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15b-5p, miR-197-3p, miR-30c-5p, miR-486-5p
Renal nephritis	$1.23\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15b-5p, miR-197-3p, miR-30c-5p, miR-486-5p
Liver tissue
Hepatocellular carcinoma	$3.99\times {10}^{-15}$–$2.44\times {10}^{-02}$	miR-99a-5p, miR-122-5p, miR-130a-3p, miR-146a-5p, miR-148a-3p, miR-15b-5p, miR-17-5p, miR-181a-5p, miR-192-5p, miR-199a-3p, miR-199a-5p, miR-221-3p, miR-27b-3p, miR-29a-3p, miR-30c-5p
Liver hyperplasia/hyperproliferation	$3.99\times {10}^{-15}$–$2.44\times {10}^{-02}$	miR-99a-5p, miR-122-5p, miR-130a-3p, miR-146a-5p, miR-148a-3p, miR-15b-5p, miR-17-5p, miR-181a-5p, miR-192-5p, miR-199a-3p, miR-199a-5p, miR-221-3p, miR-27b-3p, miR-29a-3p, miR-30c-5p
Liver inflammation/hepatitis	$1.4\times {10}^{-11}$	miR-99a-5p, miR-130a-3p, miR-15b-5p, miR-199a-5p, miR-221-3p, miR-27b-3p
Liver cirrhosis	$2.28\times {10}^{-08}$–$8.65\times {10}^{-08}$	miR-99a-5p, miR-130a-3p, miR-15b-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, miR-27b-3p
Cardiac tissue
Cardiac dilation	$8.95\times {10}^{-06}$	miR-146a-5p, miR-17-5p, miR-199a-3p, miR-30c-5p, miR-486-5p
Cardiac enlargement	$8.95\times {10}^{-06}$	miR-146a-5p, miR-17-5p, miR-199a-3p, miR-30c-5p, miR-486-5p
Congenital heart anomaly	$2.82\times {10}^{-02}$	miR-130a-3p
PCB congener-associated miRs
Renal tissue
Glomerular injury	$2.74\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15a-5p, miR-185-5p, miR-320a
Renal inflammation	$2.74\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15a-5p, miR-185-5p, miR-320a
Renal nephritis	$2.74\times {10}^{-09}$	miR-99a-5p, miR-130a-3p, miR-15a-5p, miR-185-5p, miR-320a
Liver tissue
Hepatocellular carcinoma	$2.03\times {10}^{-08}$–$1.35\times {10}^{-02}$	miR-99a-5p, miR-122-5p, miR-130a-3p, miR-15a-5p, miR-192-5p, miR-21-5p, miR-22-3p, miR-29c-3p
Liver hyperplasia/hyperproliferation	$2.03\times {10}^{-08}$–$1.35\times {10}^{-02}$	miR-99a-5p, miR-122-5p, miR-130a-3p, miR-15a-5p, miR-192-5p, miR-21-5p, miR-22-3p, miR-29c-3p
Liver inflammation/hepatitis	$3.41\times {10}^{-06}$	miR-99a-5p, miR-130a-3p, miR-15a-5p
Liver cirrhosis	$2.51\times {10}^{-04}$	miR-99a-5p, miR-130a-3p, miR-15a-5p
Cardiac tissue
Congenital heart anomaly	$1.07\times {10}^{-04}$	miR-130a-3p, miR-185-5p
Cardiac fibrosis	$2.71\times {10}^{-03}$	miR-21-5p

Note: The range for $p$-value is shown if more than one pathway is enriched for a given category. K18, Keratin 18; let, lethal; M30, K18 measured as a caspase 3-cleaved fragment; M65, K18 measured as a whole protein; miR, microRNA; PCB, polychlorinated biphenyl.