Design and experimental approach to the construction of a human signal-molecule-profiling database

Abstract

The human signal-molecule-profiling database (HSMPD) is designed as a prospective medical database for translational bioinformatics (TBI). To explore the feasibility of low-cost database construction, we studied the roadmap of HSMPD. A HSMPD-oriented tool, called "signal-molecule-profiling (SMP) chip" was developed for data acquisition, which can be employed in the routine blood tests in hospitals; the results will be stored in the HSMPD system automatically. HSMPD system can provide data services for the TBI community, which generates a stable income to support the data acquisition. The small-scale experimental test was performed in the hospital to verify SMP chips and the demo HSMPD software. One hundred and eighty nine complete SMP records were collected, and the demo HSMPD system was also evaluated in the survey study on patients and doctors. The function of SMP chip was verified, whereas the demo HSMPD software needed to be improved. The survey study showed that patients would only accept free tests of SMP chips when they originally needed blood examinations. The study indicated that the construction of HSMPD relies on the self-motivated cooperation of the TBI community and the traditional healthcare system. The proposed roadmap potentially provides an executable solution to build the HSMPD without high costs.

Figure 1

Three categories of current biomedical databases. The current biomedical databases can be roughly classified into three categories according to the origin and properties of data. HSMPD was proposed to take advantage of the healthcare system to build a prospective database for TBI. HSMPD contains large quantity of redundant information to doctors, but the information is valuable to TBI researchers.

Figure 2

Technology roadmap of HSMPD construction. HSMPD is a bridge to connect traditional health care systems with the TBI community. The HSMPD services on TBI community can provide a stable income to support the data acquisition process of HSMPD, which forms a self-motivated mechanism.

Figure 3

Data structure of HSMPD. Clinical records in HSMPD will be inputted by doctors, nurses and chip readers. The information of every record is categorized into two parts. The medical SMP data is open for all researchers and patients without unnecessary ethical review, whereas the private information of patients is protected behind firewall, which can be mediated by a trusted intermediary.

Figure 4

Structure of a SMP chip and its operation flow. (a) Gold films coated the surfaces of the poly (methyl methacrylate). Different capture antibodies for respective targets were immobilized on the gold film in every chamber. The principle of immuno-NASBA assay is similar to sandwich enzyme-linked immunosorbent assay (ELISA), however, the report group in the detector antibody is a barcode DNA with a T7 RNA polymerase promoter instead of an enzyme. The barcode DNA plays as a bridge to connect immunoassay and NASBA amplification. Then fluorescent signals will be generated in the NASBA amplification with the help of beacon probes. (b) The operation flow is proposed on the left.

Figure 5

Typical process of data acquisition in HSMPD system. (a) A flow chart above is to demonstrate the data acquisition process for HSMPD. Only 16 types of signal molecule targets were measure on the SMP chip prototype in this study. (b) The first version of HSMPD system was developed by Microsoft Access^® 2010. (c) The second version of HSMPD system was made in Microsoft^® SQL Server^® 2005.

Figure 6

Survey study in the data acquisition process of HSMPD [34]. (a) The survey result on the attitudes towards HSMPD among the people far away from hospitals. (b) The different survey result on the attitude of the public in the blood-collection room. (c) The distribution of reasons given by 143 interviewees who refused to participate in the HSMPD project. (d) The reasons and purposes of the 189 participants in the HSMPD project. (e) The points of view of the participants regarding the privacy issues of the HSMPD.

Figure 7

Comparison plots for corresponding results of both the on-chip SMP testing and traditional ELISA method. (a) Plot A showed the typical curves of on-chip immuno-NASBA assays using artificial TNF-α solutions as the standard samples. The decoding of the raw date in the curves was described before [33]. Multiple signal molecule targets in patient samples were measured on the SMP chips, while some patient samples were also quantified by the other ELISA kits. (b) The comparison plots of the test results of FSH. (c) The comparison plots of the test results of LH. (d) The comparison plots of the test results of TSH. (e) The comparison plots of the test results of HCG. (f) The comparison plots of the test results of cortisol.