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Requirements analysis and specification for a molecular tumor board platform based on cBioPortal
(2020)
Clinicians in molecular tumor boards (MTB) are confronted with a growing amount of genetic high-throughput sequencing data. Today, at German university hospitals, these data are usually handled in complex spreadsheets from which clinicians have to obtain the necessary information. The aim of this work was to gather a comprehensive list of requirements to be met by cBioPortal to support processes in MTBs according to clinical needs. Therefore, oncology experts at nine German university hospitals were surveyed in two rounds of interviews. To generate an interview guideline a scoping review was conducted. For visual support in the second round, screenshot mockups illustrating the requirements from the first round were created. Requirements that cBioPortal already meets were skipped during the second round. In the end, 24 requirements with sometimes several conceivable options were identified and 54 screenshot mockups were created. Some of the identified requirements have already been suggested to the community by other users or are currently being implemented in cBioPortal. This shows, that the results are in line with the needs expressed by various disciplines. According to our findings, cBioPortal has the potential to significantly improve the processes and analyses of an MTB after the implementation of the identified requirements.
Protein–protein interactions are at the core of all cellular functions and dynamic alterations in protein interactions regulate cellular signaling. In the last decade, mass spectrometry (MS)-based proteomics has delivered unprecedented insights into human protein interaction networks. Affinity purification-MS (AP-MS) has been extensively employed for focused and high-throughput studies of steady state protein–protein interactions. Future challenges remain in mapping transient protein interactions after cellular perturbations as well as in resolving the spatial organization of protein interaction networks. AP-MS can be combined with quantitative proteomics approaches to determine the relative abundance of purified proteins in different conditions, thereby enabling the identification of transient protein interactions. In addition to affinity purification, methods based on protein co-fractionation have been combined with quantitative MS to map transient protein interactions during cellular signaling. More recently, approaches based on proximity tagging that preserve the spatial dimension of protein interaction networks have been introduced. Here, we provide an overview of MS-based methods for analyzing protein–protein interactions with a focus on approaches that aim to dissect the temporal and spatial aspects of protein interaction networks.
Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence of the fitness of CHIP-mutated human hematopoietic stem cells (HSCs) in blood reconstitution is lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous stem cell transplantation (ASCT) for the development of CHIP. We found a high incidence of CHIP (22%) after ASCT with a high mean variant allele frequency (VAF) of 10.7%. Most mutations were already present in the graft, albeit at lower VAFs, demonstrating a selective reconstitution advantage of mutated HSCs after ASCT. However, patients with CHIP mutations in DNA-damage response genes showed delayed neutrophil reconstitution. Thus, CHIP-mutated stem and progenitor cells largely gain on clone size upon ASCT-related blood reconstitution, leading to an increased future risk of CHIP-associated complications.