1. Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI) 
Johanna Kurko, Maaria Tringham, Laura Tanner, Kirsti Näntö-Salonen, Mari Vähä-Mäkilä, Heli Nygren, Päivi Pöhö, Niina Lietzen, Ismo Mattila, Anu Olkku, Tuulia Hyötyläinen, Matej Orešič, Olli Simell, Harri Niinikoski, Juha Mykkänen 
Metabolism - Clinical and Experimental 
Volume 65, Issue 9, Pages (September 2016)
DOI: /j.metabol
Copyright © 2016 Elsevier Inc. Terms and Conditions

2. Fig. 1
Pairwise correlations of amino acids and clinical variables in LPI. The heatmap with dendrograms was computed based on the Spearman correlation coefficients calculated for each pair of variables including 17 amino acids with significantly changed levels, nitric oxide (NO)/nitrite, estimated glomerular filtration rate (eGFR), clinical variables, statin medication and supplementations in the LPI patients. Hierarchical clustering shows amino acids and other variables with the most similar pairwise-correlation patterns. The categorical variable of the patients' statin medication was annotated as following: no medication=0, medication=1. ALP, alkaline phosphatase; ALT, alanine transaminase; NH4, ammonium; LDL, low-density lipoprotein; HDL, high-density lipoprotein. The Pvalues were Benjamini–Hochberg-corrected. *P<0.05, **P<0.01, ***P<0.001.
Metabolism - Clinical and Experimental  , DOI: ( /j.metabol )
Copyright © 2016 Elsevier Inc. Terms and Conditions

3. Fig. 2
LPI patients are hierarchically clustered according to their CKD stages. The heatmap with dendrograms was computed by the log2-transferred concentration values of 58 metabolites with q<0.05 in order to hierarchically cluster LPI patients (P1-P26) and controls (C1-C19), and also metabolites. The LPI patients with the CKD stages 2–5 are indicated by both ID markings and red lines in the dendrogram. The red rectangular indicates both the cluster of metabolites correlating significantly with estimated glomerular filtration rate (eGFR) (see Fig. 3) and the cluster of the LPI patients with the most severe CKD.
Metabolism - Clinical and Experimental  , DOI: ( /j.metabol )
Copyright © 2016 Elsevier Inc. Terms and Conditions

4. Fig. 3
A group of metabolites has a high inverse correlation with kidney function in LPI. The heatmap with dendrograms was computed based on the Spearman correlation coefficients calculated for each pair of variables including 58 metabolites with significantly altered levels, nitric oxide (NO)/nitrite, estimated glomerular filtration rate (eGFR), clinical variables, statin medication and supplementations in the LPI patients. Hierarchical clustering shows metabolites and other variables with the most similar pairwise-correlation patterns. The categorical variable of the patients' statin medication was annotated as following: no medication=0, medication=1. ALP, alkaline phosphatase; ALT, alanine transaminase; NH4, ammonium; LDL, low-density lipoprotein; HDL, high-density lipoprotein. The P values were Benjamini–Hochberg-corrected. *P<0.05, **P<0.01, ***P<0.001.
Metabolism - Clinical and Experimental  , DOI: ( /j.metabol )
Copyright © 2016 Elsevier Inc. Terms and Conditions

5. Fig. 4
Pairwise correlations of the lipid clusters (LC1-LC8) and clinical variables in LPI. The heatmap with dendrograms was computed based on the Spearman correlation coefficients calculated for each pair of variables including eight lipid clusters with significantly changes levels, nitric oxide (NO)/nitrite, estimated glomerular filtration rate (eGFR), clinical variables, statin medication and supplementations in the LPI patients. Hierarchical clustering shows lipid clusters and other variables with the most similar pairwise-correlation patterns. The categorical variable of the patients' statin medication was annotated as following: no medication=0, medication=1. ALP, alkaline phosphatase; ALT, alanine transaminase; NH4, ammonium; LDL, low-density lipoprotein; HDL, high-density lipoprotein. The P values were Benjamini–Hochberg-corrected. *P<0.05, **P<0.01, ***P<0.001.
Metabolism - Clinical and Experimental  , DOI: ( /j.metabol )
Copyright © 2016 Elsevier Inc. Terms and Conditions