scholarly journals Impact of Hemolysis on Multi-OMIC Pancreatic Biomarker Discovery: Derisking Precision Medicine Biomarker Development

Author(s):  
Richard Searfoss ◽  
Punit Shah ◽  
Kennedy Ofori-Mensa ◽  
Valerie Bussberg ◽  
Vladimir Tolstikov ◽  
...  

Abstract Cancer biomarker discovery is critically dependent on the integrity of biofluid, and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0 – 10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7 year longitudinal multi-omic biomarker discovery program evaluating 400+ participants with or at risk for pancreatic cancer, known as Project Survival™. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of Buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.

2021 ◽  
Author(s):  
Richard Searfoss ◽  
Punit Shah ◽  
Kennedy Ofori-Mensa ◽  
Valerie Bussberg ◽  
Vladimir Tolstikov ◽  
...  

Abstract Cancer biomarker discovery is critically dependent on the integrity of biofluid, and tissue samples acquired from study participants. Multi-omic profiling of candidate protein, lipid, and metabolite biomarkers is confounded by timing and fasting status of sample collection, participant demographics and treatment exposures of the study population. Contamination by hemoglobin, whether caused by hemolysis during sample preparation or underlying red cell fragility, contributes 0–10 g/L of extraneous protein to plasma, serum, and Buffy coat samples and may interfere with biomarker detection and validation. We analyzed 617 plasma, 701 serum, and 657 buffy coat samples from a 7 year longitudinal multi-omic biomarker discovery program evaluating 400 + participants with or at risk for pancreatic cancer, known as Project Survival™. Hemolysis was undetectable in 93.1% of plasma and 95.0% of serum samples, whereas only 37.1% of Buffy coat samples were free of contamination by hemoglobin. Regression analysis of multi-omic data demonstrated a statistically significant correlation between hemoglobin concentration and the resulting pattern of analyte detection and concentration. Although hemolysis had the greatest impact on identification and quantitation of the proteome, distinct differentials in metabolomics and lipidomics were also observed and correlated with severity. We conclude that quality control is vital to accurate detection of informative molecular differentials using OMIC technologies and that caution must be exercised to minimize the impact of hemolysis as a factor driving false discovery in large cancer biomarker studies.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Margalida Esteva-Socias ◽  
María-Jesús Artiga ◽  
Olga Bahamonde ◽  
Oihana Belar ◽  
Raquel Bermudo ◽  
...  

Abstract The purpose of the present work is to underline the importance of obtaining a standardized procedure to ensure and evaluate both clinical and research usability of human tissue samples. The study, which was carried out by the Biospecimen Science Working Group of the Spanish Biobank Network, is based on a general overview of the current situation about quality assurance in human tissue biospecimens. It was conducted an exhaustive review of the analytical techniques used to evaluate the quality of human tissue samples over the past 30 years, as well as their reference values if they were published, and classified them according to the biomolecules evaluated: (i) DNA, (ii) RNA, and (iii) soluble or/and fixed proteins for immunochemistry. More than 130 publications released between 1989 and 2019 were analysed, most of them reporting results focused on the analysis of tumour and biopsy samples. A quality assessment proposal with an algorithm has been developed for both frozen tissue samples and formalin-fixed paraffin-embedded (FFPE) samples, according to the expected quality of sample based on the available pre-analytical information and the experience of the participants in the Working Group. The high heterogeneity of human tissue samples and the wide number of pre-analytic factors associated to quality of samples makes it very difficult to harmonize the quality criteria. However, the proposed method to assess human tissue sample integrity and antigenicity will not only help to evaluate whether stored human tissue samples fit for the purpose of biomarker development, but will also allow to perform further studies, such as assessing the impact of different pre-analytical factors on very well characterized samples or evaluating the readjustment of tissue sample collection, processing and storing procedures. By ensuring the quality of the samples used on research, the reproducibility of scientific results will be guaranteed.


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 181
Author(s):  
Ana Rita Lima ◽  
Joana Pinto ◽  
Filipa Amaro ◽  
Maria de Lourdes Bastos ◽  
Márcia Carvalho ◽  
...  

Prostate cancer (PCa) is the second most diagnosed cancer in men worldwide. For its screening, serum prostate specific antigen (PSA) test has been largely performed over the past decade, despite its lack of accuracy and inability to distinguish indolent from aggressive disease. Metabolomics has been widely applied in cancer biomarker discovery due to the well-known metabolic reprogramming characteristic of cancer cells. Most of the metabolomic studies have reported alterations in urine of PCa patients due its noninvasive collection, but the analysis of prostate tissue metabolome is an ideal approach to disclose specific modifications in PCa development. This review aims to summarize and discuss the most recent findings from tissue and urine metabolomic studies applied to PCa biomarker discovery. Eighteen metabolites were found consistently altered in PCa tissue among different studies, including alanine, arginine, uracil, glutamate, fumarate, and citrate. Urine metabolomic studies also showed consistency in the dysregulation of 15 metabolites and, interestingly, alterations in the levels of valine, taurine, leucine and citrate were found in common between urine and tissue studies. These findings unveil that the impact of PCa development in human metabolome may offer a promising strategy to find novel biomarkers for PCa diagnosis.


Methods ◽  
2015 ◽  
Vol 87 ◽  
pp. 26-30 ◽  
Author(s):  
Mu Li ◽  
Alex J. Rai ◽  
G. Joel DeCastro ◽  
Emily Zeringer ◽  
Timothy Barta ◽  
...  

2018 ◽  
Vol 29 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Steffen Moritz ◽  
Insa Happach ◽  
Karla Spirandelli ◽  
Tania M. Lincoln ◽  
Fabrice Berna

Abstract. Neurocognitive deficits in patients with mental disorders are partially due to secondary influences. “Stereotype threat” denotes the phenomenon that performance is compromised when a participant is confronted with a devaluing stereotype. The present study examined the impact of stereotype threat on neuropsychological performance in schizophrenia. Seventy-seven participants with a self-reported diagnosis of schizophrenia were randomly assigned to either an experimental condition involving stereotype threat activation or a control condition in an online study. Participants completed memory and attention tests as well as questionnaires on motivation, self-efficacy expectations, cognitive complaints, and self-stigmatization. Contrary to our prediction, the two groups showed no significant differences regarding neuropsychological performance and self-report measures. Limitations, such as a possibly too weak threat cue, are discussed and recommendations for future studies are outlined.


2021 ◽  
Vol 2 (2) ◽  
pp. 76-86
Author(s):  
Diky Setiawan ◽  
Mochammad Hasymi Somaida

The Corona virus is a virus that originates from China, and spreads rapidly throughout the world andbegan to spread to Indonesia in early March 2020. The impact of Covid-19 has caused losses in all fields,be it economy, education, etc. In the field of education, activities both learning and examinations must bereplaced online due to the impact of the spread of Covid-19. This study aims to determine theeffectiveness of the implementation of UAS which is carried out online using the Google Form applicationmedia at SMP MA'ARIF NU CIMANGGU. This research uses the quantitative survey method whichdescribes the online UAS implementation activities at SMP MA'ARIF NU CIMANGGU during thepandemic. The object consists of 35 student respondents. The data sample collection is done using aquestionnaire / questionnaire containing questions related to the implementation of UAS online using theGoogle Form application at SMP MA ' ARIF NU CIMANGGU. Based on the results of this study, theimplementation of online UAS runs effectively f and good, it can be seen from the results of satisfactorystudent scores. The application used is of course the Googke Form as the main media, and Whatsapp as amedium for interaction between teachers and students. The obstacles experienced are regarding badconnections, limited quota, schedules that frequently change, as well as difficulties in understandingsubject matter.Keywords: Covid-19,impact,effectiveness


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 907
Author(s):  
Monika Dziuba ◽  
Vickie J. Ruggiero ◽  
Catherine Wilson ◽  
Paul C. Bartlett ◽  
Paul M. Coussens

Bovine leukemia virus (BLV) is a retroviral infection that disrupts the immune function of infected animals. It is widespread among U.S. dairy cattle. In this pilot study, the average total IgA and IgM concentrations in milk, saliva, and serum samples from BLV ELISA-positive (ELISA+) dairy cows were compared against samples from BLV ELISA-negative (ELISA−) cows using the Kruskal–Wallis test (with ties). The results from ELISA+ cows were also stratified by lymphocyte count (LC) and proviral load (PVL). In milk and saliva from ELISA+ cows, the average total IgA and IgM concentrations were decreased compared to ELISA− cows, although this was only statistically significant for saliva IgM in cows with low PVL (p = 0.0424). Numerically, the average total IgA concentrations were 33.6% lower in milk and 23.7% lower in saliva, and the average total IgM concentrations were 42.4% lower in milk and 15.5% lower in saliva. No significant differences were observed in the total serum IgA concentrations, regardless of PVL and LC. The total serum IgM from ELISA+ cows was significantly decreased (p = 0.0223), with the largest decreases occurring in the highest PVL and LC subgroups. This pilot study is a first step in investigating the impact of BLV on mucosal immunity and will require further exploration in each of the various stages of disease progression.


Author(s):  
Hubert Dobrowolski ◽  
Dariusz Włodarek

The outbreak of the COVID-19 pandemic caused a number of changes in social life around the world. In response to the growing number of infections, some countries have introduced restrictions that may have resulted in the change of the lifestyle. The aim of our study was to investigate the impact of the lockdown on body weight, physical activity and some eating habits of the society. The survey involving 183 people was conducted using a proprietary questionnaire. The mean age of the study participants was 33 ± 11 and mean height 169 ± 8 cm. An average increase in body weight was observed in 49.18% by 0.63 ± 3.7 kg which was the result of a decrease in physical activity and an increase in food consumption. We also observed a decrease in PAL from 1.64 ± 0.15 to 1.58 ± 0.13 and changes in the amount of food and individual groups of products consumption, including alcohol. Among the study participants who did not lose body mass, there was an average weight gain of 2.25 ± 2.5 kg. In conclusion, an increase of weight was shown in about half of the respondents in the study group which was associated with a decrease in physical activity and an increase in the consumption of total food and high energy density products.


Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 309
Author(s):  
Zhihua Ren ◽  
Pei Gao ◽  
Samuel Kumi Okyere ◽  
Yujing Cui ◽  
Juan Wen ◽  
...  

The objective of this study was to determine the impact of Ageratina adenophora (A. adenophora) on splenic immune function in a rat model. Rats were fed with 10 g/100 g normal feed and an experimental feed, which was composed of 3:7 A. adenophora powder and normal feed for 60 days. On days 14, 28, and 60, subsets of rats (n = 8 rats/group/time point) were selected for blood and spleen tissue sample collection. The results showed that the proportion of CD3+ T cells in the spleen was decreased at day 60 (vs. control). Also, mRNA and protein expression of chemokines CCL21 and CCL19 and functional protein gp38 in spleen decreased significantly versus the control at day 60. In addition, ER-TR7 antigen protein expression was also decreased at day 60. Levels of T-helper (Th)1 cells significantly increased, whereas those of Th2 cells decreased significantly versus the control at day 60 in spleen. The finding revealed that A. adenophora could affect splenic immune function in rats by altering the fibroblast reticulocyte (FRC) network, as well as by causing an imbalance in Th1/Th2 cell ratios. This research provides new insights into potential mechanisms of spleen immunotoxicity due to exposures to A. Adenophora.


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