MedChemLens: An Interactive Visual Tool to Support Direction Selection in Interdisciplinary Experimental Research of Medicinal Chemistry.

Interdisciplinary experimental science (e.g., medicinal chemistry) refers to the disciplines that integrate knowledge from different scientific backgrounds and involve experiments in the research process. Deciding "in what direction to proceed" is critical for the success of the research in such disciplines, since the time, money, and resource costs of the subsequent research steps depend largely on this decision. However, such a direction identification task is challenging in that researchers need to integrate information from large-scale, heterogeneous materials from all associated disciplines and summarize the related publications of which the core contributions are often showcased in diverse formats. The task also requires researchers to estimate the feasibility and potential in future experiments in the selected directions. In this work, we selected medicinal chemistry as a case and presented an interactive visual tool, MedChemLens, to assist medicinal chemists in choosing their intended directions of research. This task is also known as drug target (i.e., disease-linked proteins) selection. Given a candidate target name, MedChemLens automatically extracts the molecular features of drug compounds from chemical papers and clinical trial records, organizes them based on the drug structures, and interactively visualizes factors concerning subsequent experiments. We evaluated MedChemLens through a within-subjects study (N=16). Compared with the control condition (i.e., unrestricted online search without using our tool), participants who only used MedChemLens reported faster search, better-informed selections, higher confidence in their selections, and lower cognitive load.

Learning misclassification costs for imbalanced classification on gene expression data.

BACKGROUND: Cost-sensitive algorithm is an effective strategy to solve imbalanced classification problem. However, the misclassification costs are usually determined empirically based on user expertise, which leads to unstable performance of cost-sensitive classification. Therefore, an efficient and accurate method is needed to calculate the optimal cost weights. RESULTS: In this paper, two approaches are proposed to search for the optimal cost weights, targeting at the highest weighted classification accuracy (WCA). One is the optimal cost weights grid searching and the other is the function fitting. Comparisons are made between these between the two algorithms above. In experiments, we classify imbalanced gene expression data using extreme learning machine to test the cost weights obtained by the two approaches. CONCLUSIONS: Comprehensive experimental results show that the function fitting method is generally more efficient, which can well find the optimal cost weights with acceptable WCA.

Galloyl groups-regulated fibrinogen conformation: Understanding antiplatelet adhesion on tannic acid coating.

Fibrinogen (Fgn) has been identified as the key protein in the process of biomaterial-induced platelet adhesion. We have recently reported a facile and effective method for constructing platelet-repellent surface using a natural polyphenol component tannic acid (TA). However, the mechanism by which the TA surface repels platelets was not fully understood. To address this issue, we investigated the adsorption of Fgn (amount and conformation) on four TA-functionalized surfaces with different amounts of galloyl groups and the potential for platelet adherence on these surfaces. The experimental results indicated that the four TA-functionalized surfaces adsorbed a similar amount of Fgn, but the conformation and bioactivity of the adsorbed Fgn and the subsequent platelet adherence were quite different among the surfaces. The TA surface with the most galloyl groups induced minimal changes in the conformation of Fgn, a result of the α and γ chains of the adsorbed Fgn being highly inactive on the surface, thus leading to an outstanding antiplatelet adhesion performance. With a decreased amount of galloyl groups, the activity of the α chain in the adsorbed Fgn remained unchanged, but the activity of the γ chain and the extent of platelet adhesion gradually increased. This work provided a new concept for controlling platelet adhesion on solid materials, and we envision that the TA film could have potential applications in the development of new blood-contacting biomaterials in the future. STATEMENT OF SIGNIFICANCE: Reducing platelet adhesion on material surfaces is of tremendous scientific interest in the field of blood-contacting biomaterials, but it remains a big challenge due to the highly adhesive nature of the platelets. In this study, we demonstrated for the first time that tannic acid surface with abundant galloyl groups could induce minimal conformational changes of fibrinogen, eventually leading to an outstanding antiplatelet adhesion effect. In addition, the platelet adhesion response could be easily controlled through regulating the amount of galloyl groups on the surface. This work provided a new strategy for controlling platelet adhesion on solid materials, which was totally different from existing methods such as construction of physically patterned surfaces, modification of inert hydrophilic polymers or appending bioactive moieties to target surfaces.