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DNA-encoded libraries (DELs) have emerged as an efficient and cost-effective drug discovery tool for the exploration and screening of very large chemical space using small-molecule collections of unprecedented size. Herein, we report an integrated automation and informatics system designed to enhance the quality, efficiency, and throughput of the production and affinity selection of these libraries. The platform is governed by software developed according to a database-centric architecture to ensure data consistency, integrity, and availability. Through its versatile protocol management functionalities, this application captures the wide diversity of experimental processes involved with DEL technology, keeps track of working protocols in the database, and uses them to command robotic liquid handlers for the synthesis of libraries. This approach provides full traceability of building-blocks and DNA tags in each split-and-pool cycle. Affinity selection experiments and high-throughput sequencing reads are also captured in the database, and the results are automatically deconvoluted and visualized in customizable representations. Researchers can compare results of different experiments and use machine learning methods to discover patterns in data. As of this writing, the platform has been validated through the generation and affinity selection of various libraries, and it has become the cornerstone of the DEL production effort at Lilly.

Drug combination testing in the pharmaceutical industry has typically been driven by late-stage opportunistic strategies rather than by early testing to identify drug combinations for clinical investigation that may deliver improved efficacy. A rationale for combinations exists across a number of diseases in which pathway redundancy or resistance to therapeutics are evident. However, early assays are complicated by the absence of both assay formats representative of disease biology and robust infrastructure to screen drug combinations in a medium-throughput capacity. When applying drug combination testing studies, it may be difficult to translate a study design into the required well contents for assay plates because of the number of compounds and concentrations involved. Dispensing these plates increases in difficulty as the number of compounds and concentration points increase and compounds are subsequently rolled onto additional labware. We describe the development of a software tool, in conjunction with the use of acoustic droplet technology, as part of a compound management platform, which allows the design of an assay incorporating combinations of compounds. These enhancements to infrastructure facilitate the design and ordering of assay-ready compound combination plates and the processing of combinations data from high-content organotypic assays.

Electronic laboratory notebooks (ELNs) are increasingly replacing paper notebooks in life science laboratories, including those in industry, academic settings, and hospitals. ELNs offer significant advantages over paper notebooks, but adopting them in a predominantly paper-based environment is usually disruptive. The benefits of ELN increase when they are integrated with other laboratory informatics tools such as laboratory information management systems, chromatography data systems, analytical instrumentation, and scientific data management systems, but there is no well-established path for effective integration of these tools. In this article, we review and evaluate some of the approaches that have been taken thus far and also some radical new methods of integration that are emerging.

There are technologies on the horizon that could dramatically change how informatics organizations design, develop, deliver, and support applications and data infrastructures to deliver maximum value to drug discovery organizations. Effective integration of data and laboratory informatics tools promises the ability of organizations to make better informed decisions about resource allocation during the drug discovery and development process and for more informed decisions to be made with respect to the market opportunity for compounds. We propose in this article a new integration model called ELN-centric laboratory informatics tools integration.

Aim Our aim is to evaluate the performance of a computerized virtual crossmatch within the Duke University Medical Center HLA laboratory. Our HLA lab has used virtual crossmatch (vXM) to select deceased donors for heart and lung transplantations for more than ten years, which has allowed us to accept donors from outside of our Organ Procurement Organization territory. The virtual crossmatches were done by manually checking the recipient’s HLA antibody profiles within our lab database against the potential donor’s HLA typing to identify if the recipient has any donor-specific antibodies (DSA) in the most recent serum tested and in historical sera. To ensure no DSA was missed, the vXM was manually done by multiple transplant professionals at different stages for each sensitized recipient when a donor offer was available. Laboratory informatics vendor HLA Data Systems, developers of the mTilda Lab Management System, has developed a stand-alone software program which performs a computerized vXM (cVXM) under the product name VxMatch. The VxMatch program directly connects to any HLA lab database to query required data for analysis. Methods We performed 56 cVXMs by using the new program for patients who had previously received manual vXMs (mVXM) over the past few months. 35 of the 56 patients have calculated panel reactive antibodies (cPRA) = >80%. Results We found a 100% concordance for identification of DSA between cVXM and mVXM. It took less than 5 min to complete the cVXM while the conventional mVXM took 30 min on average. For each identified unacceptable antigen, the cVXM program provides detailed information, including antibody specificities, mean fluorescence intensity (MFI), serum date and a graph showing the MFI changes of DSA over time. The mTilda cVXM can operate in two different modes: a technologist’s level and supervisory level. The supervisory module allows us to review each individual bead carrying potential unacceptable HLA antigen at alpha chain, beta chain, or allele level. This cVXM can also be used to identify the sera (for example the serum with peak DSA) for final XM and the ability to track the change of DSA post-transplant. Conclusion Our evaluation suggests that this new computerized vXM program is a user-friendly, reliable and powerful tool for HLA testing and management.

Graphical dot-matrix plots can provide the most complete and detailed comparison of two sequences. Presented here is DOTTER2, a dot-plot program for X-windows which can compare DNA or protein sequences, and also DNA versus protein. The main novel feature of DOTTER is that the user can vary the stringency cutoff interactively, so that the dot-matrix only needs to be calculated once. This is possible thanks to a ‘Greyramp tool’ that was developed to change the displayed stringency of the matrix by dynamically changing the greyscale rendering of the dots. The Greyramp tool allows the user to interactively change the lower and upper score limit for the greyscale rendering. This allows exploration of the separation between signal and noise, and fine-grained visualization of different score levels in the dot-matrix. Other useful feature are dot-matrix compression, mouse-controlled zooming, sequence alignment display and saving/loading of dot-matrices. Since the matrix only has to be calculated once and since the algorightm is fast and linear in space, DOTTER is practical to use even for sequences as long as cosmids. DOTTER was integrated in the gene-modelling module of the genomic database system ACEDB. This was done via the homology viewer BLIXEM in a way that also allows segments from the BLAST suite of searching programs to be superimposed on top of the full dot-matrix. This feature can also be used for very quick finding of the strongest matches. As examples, we analyse a Caenorhabditis elegans cosmid with several tandem repeat families, and illustrate how DOTTER can improve gene modelling.

Aim The Hema-Quebec HLA laboratory and stem cell donor registry performs HLA typing and donor search for more than 250 patients per year. We also do HLA typing for our cord blood registry (2000/year) and our stem cell donor registry (2000/year). Before February 2012, all the results from these activities and the follow up were done by paper work without informatics system support, thus increasing the risks for file loss and errors. In 2011, decision was taken to introduce a laboratory informatics system (LIS) to improve security and efficiency of the HLA laboratory and the cord blood and donor registries. Methods A French company, Inlog, was chosen to develop informatics modules which suit our needs. Three modules were developed: EdgeLab for the patient, donor, and cord blood unit HLA files; EdgeCell for the patient and donor files, the search activities, the data bank for donors, and the data bank and processing file for cord blood units; and EdgeLink to get these two first modules connected together and allow the transfer of information and results. The laboratory instruments have been interfaced and the majority of the laboratory forms have been integrated to reduce transcription. Results The EdgeLab module was implemented at the end of February 2012, following the EdgeCell module. The adaptation period for the staff extended through June 2012 where modifications to the system were needed. After this point, we could observe a clear decrease in unnecessary analysis repeats, non-conformance reports, paper work, and most of all in our turnaround time. Our delays for urgent typing could be reduced to almost half the time. A reorganization of the workflow was possible and allows us to increase our volume of HLA typing by more than 40%. Conclusions The benefit of a LIS implementation is obvious. Better control and turnaround time is achieved while the capacity of the HLA lab is increased.

Sir, Pathology informatics is now recognized as an important component of pathology training.[1,2] Learning objectives and rotations in informatics have been established in an effort to train pathology residents.[3,4] Educated residents and formally trained informatics fellows play an important role in the future of this specialty. However, the success of pathology informatics also relies on the competencies of their allies (pathology assistants, cytotechnologists, medical technologists) in informatics. While the American Society of Clinical Pathologists (ASCP) offers some informatics training to medical technologists through its “Qualification in Laboratory Informatics” program, unfortunately insufficient attention has been dedicated toward training the various technologists in the field of pathology. The Anisa I. Kanbour School of Cytotechnology at the University of Pittsburgh Medical Center (UPMC) recently updated their curriculum to include a course in informatics for its cytotechnology students. The hospital-based, 12-month program for postbaccalaureate biology graduates has traditionally been based mainly on training in morphology and limited to ancillary studies. However, in order to keep abreast with changes in the practice of cytopathology (e.g., molecular pathology and informatics),[5,6] modifications of the curriculum were deemed necessary to reflect current practices. In addition to keeping pace with evolving technologies in the field, impetus for this change in cytotechnology student training was partially market driven. Demands for new graduates who have a more diverse technical background than just morphologic skills are more desirable first-hires. In response to changing skill requirements, the American Society of Cytopathology (ASC) published a white paper in 2010 regarding the future needs of the profession.[7] The ASC commissioned the Forbes group whose findings outlined forces that might lead to the emergence of new professions or roles in cytology. The group emphasized the need to create new skills and expanding traditional roles merging morphologic skills with new technologies for the profession's survival. Professional predictions of traditional microscopy obsolescence, new guidelines calling for less frequent Pap testing, and the digitization of proficiency testing[8] necessitated course modernization. As a result, eight cytotechnology students were exposed to pathology informatics practices and technologies in the form of an interactive 2-day course. To the best of our knowledge, the school of cytotechnology at UPMC is currently the first of 31 accredited programs in the USA to offer a structured, formal informatics course. The course was provided by the collaborative effort between the school of cytotechnology and informatics division in the department of pathology. The goals of this course were to introduce the students to the fundamentals of pathology informatics (e.g., terminology, basic computing, coding, data management, etc.), explain and demonstrate to them various information technologies (e.g., laboratory information systems, digital imaging, telecytology, etc.), and offer them “hands-on” experiences (e.g., scanning glass slides to create whole slide images, perform internet literature searches). Students were required to construct a presentation of an interesting case in which they inserted both static and virtual images into the final report. The course was well received by the students who completed a questionnaire about it. The course evaluations indicated the participants’ overall satisfaction, with only slight reservation concerning the impact informatics will play in their future practices. Following the course, students were more comfortable with digital imaging, and even able to access the institution's digital slide teaching sets in preparation for their final examinations [Figure 1]. While informatics training may be considered important by many technologist training programs, inadequate resources and lack of formal, structured programs may limit training. Therefore, we recommend that programs begin to partner with pathology departments who have informatics resources to leverage their faculty and equipment such as whole slide scanners. In the near future we can anticipate that well-trained cytotechnologists will begin to fill a niche for informatics within pathology departments. Figure 1 Example of a digital slide teaching set for cytotechnology students

Genetic medicine is poised to revolutionise healthcare. No medical specialty field will be more transformed by the use of genetic technology and genetic knowledge than pathology and laboratory medicine. To help pathologists and laboratory professionals understand the strategic implications of these developments, this presentation will provide an overview of how health system dynamics, financial considerations, and advances in genetic technology will drive forward the clinical acceptance and use of molecular technologies in pathology testing services. Themes to be discussed include how new genetic technologies will be incorporated into diagnostic testing services, market adoption paths for personalised medicine and companion diagnostics, and the role of laboratory informatics in linking laboratories with referring clinicians. Opportunities for pathology to participate as a collaborative diagnostic service will be identified. Pathologists will gain a strategic understanding of the major trends in healthcare and how these trends will support advancements in molecular diagnostics. Information and concepts presented will complement the presentations which follow during this session.