Transcriptome and ribosome sequencing have revealed the existence of many non-canonical transcripts, mainly containing splice variants, ncRNA, sORFs and altORFs. However, identification and characterization of products that may be translated out of these remains a challenge. Addressing this, we here report on 552 non-canonical proteins and splice variants in the model organism C. elegans using tandem mass spectrometry. Aided by sequencing-based prediction, we generated a custom proteome database tailored to search for non-canonical translation products of C. elegans. Using this database, we mined available mass spectrometric resources of C. elegans, from which 51 novel, non-canonical proteins could be identified. Furthermore, we utilized diverse proteomic and peptidomic strategies to detect 40 novel non-canonical proteins in C. elegans by LC-TIMS-MS/MS, of which 6 were common with our meta-analysis of existing resources. Together, this permits us to provide a resource with detailed annotation of 467 splice variants and 85 novel proteins mapped onto UTRs, non-coding regions and alternative open reading frames of the C. elegans genome.

This abstract is a report of the investigations by a transdisciplinary team working on the ‘Vaccine Confidence’ challenge (Supplement 1). Since their introduction, vaccines have been one of the most successful health interventions in medicine. Prior to vaccination programs against poliomyelitis, more than 350,000 cases of polio were reported annually worldwide, a number that decreased to just 33 reported cases in 20181. Additionally, between 2000 and 2017, the measles vaccination program is estimated to have prevented 21.1 million deaths.2 However, in 2018 more than 19 million children under one year of age did not receive the recommended WHO vaccines.3 A recent rise in anti-vaccine or vaccination-hesitant mentalities has led to decreasing vaccine coverage in several Western countries. The WHO identified three C’s as main determinants of vaccine hesitancy, namely Complacency, Convenience in accessing vaccines, and Confidence. However, the term ‘vaccine hesitancy’ tends to be interpreted as a lack of confidence in vaccines and vaccinations for various reasons. Nevertheless, the goal of vaccination is to reach herd immunity by reaching a high vaccination coverage (90‐95% vaccinated) to stop the circulation of vaccine preventable diseases. We wanted to give equal attention to the three C’s as they are equally important in reaching herd immunity. <target target-type="page-num" id="p-116"/>Therefore, we chose to present the problem as a challenge of ‘vaccine coverage,’ rather than ‘vaccine hesitancy’ or ‘vaccine confidence’. In order to understand the complexity of the problem, we have developed a systems map which relates different global factors that impact an individual’s vaccination decision-making, as well as their likelihood of receiving vaccinations (Supplement 2). To create this map we assembled the information for the variables and connections from literature studies of peer-reviewed articles and interviews with stakeholders, kept anonymous, in the field of vaccination or healthcare (Supplements 3 & 4). This approach was selected as it provides a wide perspective that allows academics, governmental authorities, and lawmakers to better assess the various factors that affect vaccine coverage, and how they are related. The work leading to the map was presented to the public at a symposium (Supplement 5). Our map identifies essential factors such as psychology, education, economy, vaccine technology, political and environmental sphere, sources of information, and healthcare in order to understand what governs vaccination coverage. The map emphasizes how various factors and determinants are often interrelated, as opposed to the isolated factors described in previous literature. We identified important discrepancies between developed and developing countries regarding the factors that drive vaccine-related decision-making and availability. The systems map could ultimately serve as a tool to better understand the multifaceted problem of suboptimal vaccination coverage. Vaccine hesitancy as a threat to vaccination coverage is a complex and wicked problem with many underlying contributing factors, as has been depicted in our systems map on vaccine coverage. Our systems map allows more in-depth insights, not only into which factors are contributing, but also into the relationship between factors. Solving the decrease in vaccination coverage will require different types of solutions which can be developed by using a transdisciplinary approach.