Graph Node Classification to Predict Autism Risk in Genes.

This study explores the genetic risk associations with autism spectrum disorder (ASD) using graph neural networks (GNNs), leveraging the Sfari dataset and protein interaction network (PIN) data. We built a gene network with genes as nodes, chromosome band location as node features, and gene interactions as edges. Graph models were employed to classify the autism risk associated with newly introduced genes (test set).

Evolving approaches on measurements and applications of intracellular free drug concentration and Kp in drug discovery.

: Intracellular-free drug concentration (C) and unbound partition coefficient (Kp) are two important parameters to develop pharmacokinetic and pharmacodynamic relationships, predict drug-drug interaction potentials and estimate therapeutic indices.: Methods on measurements of C, Kp partition coefficient (Kp) and fraction unbound of cells (f) are discussed. Advantages and limitations of several f methods are reviewed.

Mechanistic insights on clearance and inhibition discordance between liver microsomes and hepatocytes when clearance in liver microsomes is higher than in hepatocytes.

Human liver microsomes (HLM) and human hepatocytes (HHEP) are two common in vitro systems used in metabolic stability and inhibition studies. The comparison between the assays using the two systems can provide mechanistic insights on the interplay of metabolism, passive permeability and transporters. This study investigated the critical factors impacting the unbound intrinsic clearance (CL) and IC of CYP3A inhibition between HLM and HHEP.

Comparison of Fraction Unbound Between Liver Homogenate and Hepatocytes at 4°C.

Fraction unbound (f) values obtained from liver or hepatocyte homogenate with equilibrium dialysis (f) or the hepatocyte partition coefficient method at 4°C (f) are both frequently used to estimate unbound drug concentrations (C) and unbound partition coefficient (Kp) of the liver. Literature data are somewhat controversial on this topic: some reported that the two methods gave comparable f values, while others showed that they had no correlation. To better understand the two approaches, 44 structurally diverse compounds with wide ranges of f values were used for the comparison study.