Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery

<p>Abstract</p> <p>Background</p> <p>There is an important need for the identification of novel serological biomarkers for the early detection of cancer. Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics.</p> <p>Methods</p> <p>Previous studies have focused on either gene or protein expression databases for the identification of candidates. We developed a strategy that mines six publicly available gene and protein databases for tissue-specific proteins, selects proteins likely to enter the circulation, and integrates proteomic datasets enriched for the cancer secretome to prioritize candidates for further verification and validation studies.</p> <p>Results</p> <p>Using colon, lung, pancreatic and prostate cancer as case examples, we identified 48 candidate tissue-specific biomarkers, of which 14 have been previously studied as biomarkers of cancer or benign disease. Twenty-six candidate biomarkers for these four cancer types are proposed.</p> <p>Conclusions</p> <p>We present a novel strategy using bioinformatics to identify tissue-specific proteins that are potential cancer serum biomarkers. Investigation of the 26 candidates in disease states of the organs is warranted.</p

Parent-youth agreement on psychiatric diagnoses and symptoms: results from an adolescent outpatient clinical sample.

To access publisher's full text version of this article click on the hyperlink belowObjective: Previous research suggests that agreement, between youths and their parents, regarding assessment of youth psychiatric problems is limited. Due to this discrepancy, a multi-informant, multimethod approach is recommended when gathering psychopathological information. This study examines parent-youth agreement regarding youth psychiatric problems. It does so at a diagnostic level and at a symptom level, as well as studying the influence of age, gender, depressive disorder, anxiety disorder and attention-deficit/hyperactivity disorder (ADHD) as potential moderators of agreement. Methods: The participants in this study were 61 adolescents aged 12-18 years and their parents. The K-SADS-PL DSM-5 was administered in two outpatient units, with adolescents and their parents interviewed separately. Participants also rated symptoms using a broad rating scale (Child Behavior Checklist and the Youth Self-Report) prior to being interviewed. Results: Parent-youth agreement at a diagnostic level ranged from fair to excellent. Agreement at a symptom level was lower than that at a diagnostic level, ranging from poor to fair. These results indicate that parent-youth agreement regarding diagnosis and symptoms is higher than in most previous studies. The results also suggest that some variables, such as age, gender, depressive disorders, and ADHD, potentially influence agreement on symptoms. Conclusion: These findings support the importance of gathering information from both children and parents, and that clinicians should consider moderating factors when integrating data from multiple informants. Keywords: Agreement; assessment; children; parent–youth agreement; schedule for affective disorders and schizophrenia for school-age children Kiddie-SADS-PL (K-SADS).University of Iceland Research Fun

Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co-regulate proteasomes and mitochondria.

Mutations in FBXO7 have been discovered to be associated with an atypical parkinsonism. We report here a new homozygous missense mutation in a paediatric patient that causes an L250P substitution in the dimerisation domain of Fbxo7. This alteration selectively ablates the Fbxo7-PI31 interaction and causes a significant reduction in Fbxo7 and PI31 levels in patient cells. Consistent with their association with proteasomes, patient fibroblasts have reduced proteasome activity and proteasome subunits. We also show PI31 interacts with the MiD49/51 fission adaptor proteins, and unexpectedly, PI31 acts to facilitate SCFFbxo7 -mediated ubiquitination of MiD49. The L250P mutation reduces the SCFFbxo7 ligase-mediated ubiquitination of a subset of its known substrates. Although MiD49/51 expression was reduced in patient cells, there was no effect on the mitochondrial network. However, patient cells show reduced levels of mitochondrial function and mitophagy, higher levels of ROS and are less viable under stress. Our study demonstrates that Fbxo7 and PI31 regulate proteasomes and mitochondria and reveals a new function for PI31 in enhancing the SCFFbxo7 E3 ubiquitin ligase activity.This work is supported by funding from the BBSRC DTP to LS and HL, a Parkinson’s UK grant (G-1701) to RAB, MZ and HL, and a Rosetrees Trust Project Grant (PGL22/100035) to SAR, RAB, and HL. This research is also supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014, including the Cell Phenotyping Hub. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This research was funded in whole, or in part, by the Wellcome Trust 203151/Z/16/Z. NQM is supported by the Francis Crick Institute, which receives its core funding (FC001115) from Cancer Research UK, the UK Medical Research Council and the Wellcome Trust

Study of an <i>FBXO7</i> patient mutation reveals Fbxo7 and <scp>PI</scp>31 co‐regulate proteasomes and mitochondria

Publication status: PublishedFunder: Medical Research Council; doi: http://dx.doi.org/10.13039/501100000265Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268Mutations in FBXO7 have been discovered to be associated with an atypical parkinsonism. We report here a new homozygous missense mutation in a paediatric patient that causes an L250P substitution in the dimerisation domain of Fbxo7. This alteration selectively ablates the Fbxo7‐PI31 interaction and causes a significant reduction in Fbxo7 and PI31 levels in patient cells. Consistent with their association with proteasomes, patient fibroblasts have reduced proteasome activity and proteasome subunits. We also show PI31 interacts with the MiD49/51 fission adaptor proteins, and unexpectedly, PI31 acts to facilitate SCFFbxo7‐mediated ubiquitination of MiD49. The L250P mutation reduces the SCFFbxo7 ligase‐mediated ubiquitination of a subset of its known substrates. Although MiD49/51 expression was reduced in patient cells, there was no effect on the mitochondrial network. However, patient cells show reduced levels of mitochondrial function and mitophagy, higher levels of ROS and are less viable under stress. Our study demonstrates that Fbxo7 and PI31 regulate proteasomes and mitochondria and reveals a new function for PI31 in enhancing the SCFFbxo7 E3 ubiquitin ligase activity.</jats:p