Quality Control Standards Research Articles

The decay of Six Sigma and the rise of Quality 4.0 in manufacturing innovation

Smart manufacturing (SM) processes exhibit rapidly increasing complexity, nonlinear patterns in hyperdimensional spaces, high volumes of data, transient sources of variations, reduced lifetime, ultrahigh conformance, and non-Gaussian pseudo-chaotic behaviors. Standard quality control techniques and paradigms are not up to handling all these dynamics. Therefore, quality engineers went stagnant, with little innovation to offer to the manufacturing industry. Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL) have been applied to solve complex engineering problems and drive innovation. This new era where computer science principles are applied to quality control is called Quality 4.0 (Q4.0). However, the Six Sigma five-step problem-solving strategy (define, measure, analyze, improve, and control) does not fit the full ML cycle. The limitations of the Six Sigma techniques and paradigms in driving manufacturing innovation are discussed. A case study where a 3D quality pattern that can be easily detected by an MLA is not detected by traditional process monitoring methods. Early results motivate the development of the new era of Q4.0 without the limitations of Six Sigma and the potential of AI.

Genome-wide association study for carcass weight in pasture-finished beef cattle in Hawai'i.

Introduction: Genome-wide association studies (GWAS) have identified genetic markers for cattle production and reproduction traits. Several publications have reported Single Nucleotide Polymorphisms (SNPs) for carcass-related traits in cattle, but these studies were rarely conducted in pasture-finished beef cattle. Hawai'i, however, has a diverse climate, and 100% of its beef cattle are pasture-fed. Methods: Blood samples were collected from 400 cattle raised in Hawai'i islands at the commercial harvest facility. Genomic DNA was isolated, and 352 high-quality samples were genotyped using the Neogen GGP Bovine 100K BeadChip. SNPs that did not meet the quality control standards were removed using PLINK 1.9, and 85k high-quality SNPs from 351 cattle were used for association mapping with carcass weight using GAPIT (Version 3.0) in R 4.2. Four models were used for the GWAS analysis: General Linear Model (GLM), the Mixed Linear Model (MLM), the Fixed and Random Model Circulating Probability Unification (FarmCPU), the Bayesian-Information and Linkage-Disequilibrium Iteratively Nested Keyway (BLINK). Results and Discussion: Our results indicated that the two multi-locus models, FarmCPU and BLINK, outperformed single-locus models, GLM and MLM, in beef herds in this study. Specifically, five significant SNPs were identified using FarmCPU, while BLINK and GLM each identified the other three. Also, three of these eleven SNPs ("BTA-40510-no-rs", "BovineHD1400006853", and "BovineHD2100020346") were shared by multiple models. The significant SNPs were mapped to genes such as EIF5, RGS20, TCEA1, LYPLA1, and MRPL15, which were previously reported to be associated with carcass-related traits, growth, and feed intake in several tropical cattle breeds. This confirms that the genes identified in this study could be candidate genes for carcass weight in pasture-fed beef cattle and can be selected for further breeding programs to improve the carcass yield and productivity of pasture-finished beef cattle in Hawai'i and beyond.

Parsing the Q-Markers of Baoyin Jian to Treat Abnormal Uterine Bleeding by High-Throughput Chinmedomics Strategy.

Abnormal uterine bleeding (AUB) is a common and frequently occurring disease in gynecology, seriously threatening women's health. Baoyin Jian (BYJ) is a classical prescription for treating AUB. However, the lack of quality control standards of BYJ for AUB have limited the development and applications of BYJ. This experiment aims to explore the mechanism of action and screen the quality markers (Q-markers) of BYJ against AUB through the Chinmedomics strategy to improve the quality standards of Chinese medicine and provide scientific basis for its further development. BYJ has hemostatic effects in rats, as well as the ability to regulate the coagulation system following incomplete medical abortion. According to the results of histopathology, biochemical indexes and urine metabolomics, a total of 32 biomarkers of ABU in rats were identified, 16 of which can be significantly regulated by BYJ. Using traditional Chinese medicine (TCM) serum pharmacochemistry technology, 59 effective components were detected in vivo, of which 13 were highly correlated with efficacy, and 9 components, namely catalpol, rehmannioside D, paeoniflorin, berberine, phellodendrine, baicalin, asperosaponinVI, liquiritin, and glycyrrhizic acid, were screened out as the Q-markers of BYJ based on the "Five Principles" of Q-markers. In sum, BYJ can effectively alleviate abnormal bleeding symptoms and metabolic abnormalities in AUB rats. The study shows that Chinmedomics is an effective tool for screening Q-markers and provides scientific support for the further development and clinical use of BYJ.

Analisis Ketepatan Pemberian Opini Akuntan Publik di Indonesia

Purpose: This study aims to explain the problem of the accuracy of giving opinions given by public accountants in Indonesia, using framing theory analysis. In this study we developed an analysis of the accuracy of opinions in which we observed matters that were the causes of non-compliance by public accountants, so as to be able to provide more complex and in-depth information to understand attitudes, perceptions, emotions, beliefs about the motives and behavior of informants. Methodology: The informants for this study were 12 Public Accountants who had permission from the Ministry of Finance of the Republic of Indonesia to sign the Independent Auditor's Report. Data collection techniques were using semi-structured interviews, testing the validity of the data using the triangulation method and analyzing and processing data using Nvivo software version 12. Results: The results of the study show that the accuracy of giving a Public Accountant's opinion is influenced by: Auditor, Client Integrity, Public Accountant Integrity and Audit Planning. The violation committed by the Public Accountant is giving an opinion that is not in accordance with the actual situation, due to: not complying with Standard Auditing (SA) 230 regarding Audit Documentation, not complying with SA 500 Audit Evidence, providing audit services not through KAP, providing audit services but the license has been revoked, audit reports are not supported by working papers, receive audit assignments that are being audited by another KAP, have not complied with SA 510 Initial Balances, have not implemented Quality Control Standards, have not fully reported audit clients, and have not maintained working papers. Limitations: This study examines the existence of Framing Theory, Auditing understanding, and the problems of the practice of the Public Accountant Profession regarding the implementation of Professional Ethics and Laws. To provide input to the practice of Public Accountants that in carrying out practices must be in accordance with Auditing Standards and applicable rules.

Relative estimation of beta-sitosterol in alcoholic extracts of roots and small branches of oroxylum indicum (L.) Kurz by HPTLC for plant part substitution, medicinal uses and conservation

Beta-sitosterol is a common and useful ‘phytosterol’, present in roots and small branches of Oroxylum indicum (L.) Kurz It has mainly cholesterol-lowering, anti-inflammatory, anti-cancer, and dietary properties. O. indicum is a rare medicinal plant in the traditional medicine system. This study comparatively identified and estimated beta-sitosterol in the methanolic extracts of roots and the small branches of O. indicum by the development of a validated HPTLC method. Chromatographic separation was performed on precoated TLC plates by toluene: ethyl acetate: formic acid: water (6:3:1:0.2, v/v/v/v) with standard procedures using HPTLC assembly. Marker was identified at RF 0.60 as prominent bands and quantified at 540 nm with sharp peaks corresponding to beta-sitosterol by calibration method. The method was validated as per ICH guidelines with a good linear relationship i.e. r2 = 0.9973 ± 0.000405 in 100 – 500 ng band−1 with respect to the peak area. The LOD and LOQ were calculated as 35.22 and 106.73 ng/band, respectively. The quantity of marker in extracts of roots and the small branches was found to be 268.7% w/w and 208.5% w/w respectively in 0.5 g of the sample. The method was simple, accurate, and reproducible for rapid screening and quantification of beta-sitosterol in roots and aerial parts of O. indicum. The study may helpful for plant part substitution study, medicinal practises, sustainability, and conservation of such vulnerable plant species. It may useful to establish the quality and efficacy of plant in traditional applications and in routine standardization (quality control) of different commercial preparations of O. indicum.

Toward surface defect detection in electronics manufacturing by an accurate and lightweight YOLO-style object detector

In electronics manufacturing, surface defect detection is very important for product quality control, and defective products can cause severe customer complaints. At the same time, in the manufacturing process, the cycle time of each product is usually very short. Furthermore, high-resolution input images from high-resolution industrial cameras are necessary to meet the requirements for high quality control standards. Hence, how to design an accurate object detector with real-time inference speed that can accept high-resolution input is an important task. In this work, an accurate YOLO-style object detector was designed, ATT-YOLO, which uses only one self-attention module, many-scale feature extraction and integration in the backbone and feature pyramid, and an improved auto-anchor design to address this problem. There are few datasets for surface detection in electronics manufacturing. Hence, we curated a dataset consisting of 14,478 laptop surface defects, on which ATT-YOLO achieved 92.8% mAP0.5 for the binary-class object detection task. We also further verified our design on the COCO benchmark dataset. Considering both computation costs and the performance of object detectors, ATT-YOLO outperforms several state-of-the-art and lightweight object detectors on the COCO dataset. It achieves a 44.9% mAP score and 21.8 GFLOPs, which is better than the compared models including YOLOv8-small (44.9%, 28.6G), YOLOv7-tiny-SiLU (38.7%, 13.8G), YOLOv6-small (43.1%, 44.2G), pp-YOLOE-small (42.7%, 17.4G), YOLOX-small (39.6%, 26.8G), and YOLOv5-small (36.7%, 17.2G). We hope that this work can serve as a useful reference for the utilization of attention-based networks in real-world situations.

Analisis Keberlanjutan Usaha Padi Sawah Di Kecamatan Tugumulyo Kabupaten Musi Rawas Provinsi Sumatera Selatan Analisis

This study aims to determine the sustainability status and sensitive attributes of each dimension in lowland rice cultivation in Tugumulyo District, Musi Rawas Regency, South Sumatra Province. This research was conducted in September - October 2021 in Tugumulyo District, Musi Rawas Regency, South Sumatra Province. Sustainability analysis is carried out using Multi Dimensional Scaling analysis which consists of 5 dimensions, namely ecological, socio-cultural, economic, technological and infrastructure, as well as legal and institutional dimensions. The results showed that the multidimensional sustainability index value of paddy farming in Tugumulyo District was 44.30 with a less sustainable status. Ecological, economic, socio-cultural as well as legal and institutional dimensions have a sustainability status classified as less sustainable. While the dimensions of technology and infrastructure are quite sustainable. Sensitive attributes on the ecological dimension include the suitability of paddy fields, the use of organic fertilizers and biological/biological pesticides. Sensitive attributes on the economic dimension include the incidence of crop failure, labor fees for farming, the availability of labor if needed and the price of pesticides for paddy rice farming. Sensitive attributes on the socio-cultural dimension include water conflicts between farmers or the practice of swift water pools, the level of labor absorption from rice farming, farmers' knowledge of calm lowland rice cultivation techniques and a culture of mutual cooperation in lowland rice cultivation such as cleaning irrigation canals. Sensitive attributes on the technology and infrastructure dimensions include the availability of supporting tools for lowland rice farming, availability of seeds, fertilizers, and pest control drugs for lowland rice diseases, standardization of rice quality and operational control of lowland rice cultivation tools. Sensitive attributes on the legal and institutional dimensions are the availability of microfinance schemes for lowland rice farming, the local government's budget for lowland rice farming and the presence of water regulatory officers.

Implementasi Metode Six Sigma Dalam Pengendalian Kualitas Produksi Di Industri Tekstil Sarung Tenun (Studi Kasus: Ud. Boi Tulus)


 Boi Tulus in Balige is one of the industries engaged in the processing of woven sarongs. In order for a product to be said to be of high quality, the product must meet the specifications that have been set. To obtain a quality product, a quality control measure is needed. Quality control carried out at UD. Boi Tulus has not been carried out optimally on woven sarong products. There are obstacles that result in the quality of the woven sarong products that are not in accordance with standards, such as the discovery of defects. For that, a quality improvement action is needed at UD. Boi Tulus so as to be able to produce quality sarong products. The use of the Six Sigma method in quality control at UD. Boi Tulus is the right step in dealing with the problems faced in the industry. Based on data processing, the percentage of defects in woven sarong products at UD. Boi Tulus for the period May 2021-March 2022 is 5-9%. By using the DMAIC approach, there are 4 categories of defects in the weaving gloves, namely uneven color defects, sizes not according to specifications, torn thread defects, broken thread defects or knots. After calculating the value of DPMO on UD. Boi Tulus is 10,884 with a Sigma level value of 3,800. This means that from a million opportunities, there will be a possibility of 10,884 UD. Boi Tulus, can not meet the quality control standards carried out. Furthermore, fishbone tools are used to analyze the factors causing defects in weaving gloves, then recommendations for improvement are given in the form of SOPs and supervision is carried out in the form of control check sheets. After implementation, there are changes, namely a decrease in the value of DPMO to 4.462 and the Sigma level to 4.1239.
 
 
 Keywords : Quality Control, Defect, DMAIC, Six Sigma

Evaluating non-targeted analysis methods for chemical characterization of organic contaminants in different matrices to estimate children's exposure.

Children are vulnerable to environmental exposure of contaminants due to their small size, lack of judgement skills, as well as their proximity to dust, soil, and other environmental sources. A better understanding about the types of contaminants that children are exposed to or how their bodies retain or process these compounds is needed. In this study, we have implemented and optimized a methodology based on non-targeted analysis (NTA) to characterize chemicals in dust, soil, urine, and in the diet (food and drinking water) of infant populations. To evaluate potential toxicological concerns associated with chemical exposure, families with children between 6 months and 6 years of age from underrepresented groups were recruited in the greater Miami area. Samples of soil, indoor dust, food, water, and urine were provided by the caregivers, prepared by different techniques (involving online SPE, ASE, USE, QuEChERs), and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Data post-processing was performed using the small molecule structure identification software, Compound Discoverer (CD) 3.3, and identified features were plotted using Kendrick mass defect plot and Van Krevelen diagrams to show unique patterns in different samples and regions of anthropogenic compound classifications. The performance of the NTA workflow was evaluated using quality control standards in terms of accuracy, precision, selectivity, and sensitivity, with an average of 98.2%, 20.3%, 98.4% and 71.1%, respectively. Sample preparation was successfully optimized for soil, dust, water, food, and urine. A total of 30, 78, 103, 20 and 265 annotated features were frequently identified (detection frequency >80%) in the food, dust, soil, water, and urine samples, respectively. Common features detected in each matrix were prioritized and classified, providing insight on children's exposure to organic contaminants of concern and their potential toxicities. Current methods to assess the ingestion of chemicals by children have limitations and are generally restricted by specific classes of targeted organic contaminants of interest. This study offers an innovative approach using non-targeted analysis for the comprehensive screening of organic contaminants that children are exposed to through dust, soil, and diet (drinking water and food).

Expert consensus on the clinical application of totally implantable venous access devices in the upper arm (2022 Edition)

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

Rare TMEM230 Variants are Potentially Associated With Early Onset Parkinson’s Disease (P3-11.013)

Rare TMEM230 Variants are Potentially Associated With Early Onset Parkinson’s Disease (P3-11.013)

Research Progress on Mesenchymal Stem Cells for the Treatment of Diabetes and Its Complications.

Diabetes mellitus (DM) is a chronic disease that threatens human health. Although many drugs are available to treat DM, various complications caused by DM are unavoidable. As an emerging treatment for DM, mesenchymal stem cells (MSCs) have shown many advantages and are gradually gaining public attention. This review summarizes the clinical studies on the use of MSCs to treat DM and the potential mechanisms of complications such as pancreatic dysfunction, cardiovascular lesions, renal lesions, neurological lesions, and trauma repair. This review focuses on the research progress on MSC-mediated secretion of cytokines, improvements in the microenvironment, repair of tissue morphology, and related signaling pathways. At present, the sample sizes in clinical studies of MSCs in treating DM are small, and there is a lack of standardized quality control systems in the preparation, transportation, and infusion methods, so we need to conduct more in-depth studies. In conclusion, MSCs have shown superior potential for use in the treatment of DM and its complications and will hopefully become a novel therapeutic approach in the future.

Physicochemical evaluation of Prinsepia utilis seed oil (PUSO) and its utilization as a base in pharmaceutical soap formulation

This study aims to evaluate the standard physicochemical parameters, such as iodine value, acid value, saponification value, ester value, refractive index, peroxide value, and viscosity, of Prinsepia utilis (P. utilis) seed oil (PUSO) obtained as hexane extract from seeds, and to formulate ketoconazole soap (2% w/w) by using extracted oil as a base. The quality control standards of the final ketoconazole soap complied with the standards specified in Indian Pharmacopeia. Pharmaceutical soap was obtained by treating PUSO with potassium hydroxide (KOH), undergoing basic saponification. All physicochemical parameters, such as acid value (21.78 mg KOH/g), saponification value (194.13 mg KOH/g), iodine value (99.7 g I2/100 g), ester value (172.35 mg KOH/g), refractive index (1.464), and viscosity (192 centipoises [cps]), conformed to industrial standards, except the peroxide value (19.23 milliequivalent KOH/g). Besides, evaluation of quality control parameters of pharmaceutical soap suggested that its various parameters, such as pH (7.3), foam-forming ability (14.5 cm), foam retention time (15 min), total fatty matter (69.31%), moisture content (10.35%), and drug content (99.37%), were within the acceptable limit. Overall, our study showed that P. utilis base was physicochemically stable and suitable for manufacturing cosmetic products, soaps, and shampoo in an economical manner, rather than using expensive chemical additives, in the pharmaceutical and cosmeceutical industry. Further, this study suggested that therapeutically and commercially successful ketoconazole soap, with all the required quality control parameters, could be manufactured by using naturally available oil at a low cost.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice

Cistanche deserticola Y. C. Ma (CD), known as “desert ginseng”, has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5′-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Comparative analysis of buffalo and cow milk for quality characteristics and β-N-acetyl-glucosaminidase activity in non-infected animals

In Pakistan, milk quality control standards are yet to be established. The prime objective of this study was to develop the standard referencevalues for the milk pH, its somatic cell count (SCC), electric conductivity (EC) and NAGase i.e., milk enzyme in the noninfected milk of localbuffalo breed i.e., Nilli-Ravi also known as Black-gold of Pakistan and cows i.e., Sahiwal and other crossbred cows kept locally mostly formilch purpose. A total of 30 animals with lactation number 1-5 (in early lactation of two months) from each breed group were selectedfor milk samples. Samples were then tested for mastitis through Surf Field Mastitis test and microbiological culturing. Reference valueswere determined using negative samples. Fore-mentioned parameters were analyzed for collected Milk samples. The values for NAGaseand SCC were the most eminent in the crossbred cow’s milk i.e., (56.07±2.33 U/mL) & (178645.83±2324.0/mL) respectively. EC value(5.7±0.04) was strikingly high in Sahiwal cow’s milk. Milk of Nilli-Ravi was found superior in quality, based on its lower values of SSC,EC and NAGase. Mean values of each parameter were also compared among different quarters and found to be statistically similar. Inconclusion, milk of Nilli-Ravi was found superior in quality and current findings can be used to provide base line information for NAGaseand other components of milk quality and udder health for above mentioned dairy types.

Refuse-derived fuel-3 production simulation using network flow modeling: Predicting the uncertainty in quality standards

Municipal solid waste management requires intelligent and integrated decision-making to achieve sustainable waste treatment processes. In particular, a waste treatment system that transforms municipal solid wastes into a commodity called refuse-derived fuel (RDF) is being researched as a promising waste to energy solution. This waste processing faces limitations in maintaining consistent production and quality control standards of RDF. In this context, a network flow modeling technique is used to design a stochastic discrete-event simulation model for the production in a general material recovery facility (MRF) to evaluate its performance. The developed model supports revisions in the strategic, tactical, and operational decision levels and is integrated with varied uncertainties like probability distributions of in-feed waste compositions, moisture content, and calorific value of individual waste components, affecting the energy performance of a MRF. The model provides improvements to operating conditions and enables prediction for quality standards of RDF, enabling the waste management authority to meet their outlined quality specification for the final product. The validation of the model is conducted in a way, where the quality measures of the final product collected from an MRF are compared with the estimated values those from the simulation. The comparison reveals that precision in results from the developed model, in all performed tests is consistent with actual observed results, inferring the developed simulation model as a viable tool for estimating quality measures for RDF. The foundations of the model are based of assumptions like emphasis on general representation but not physical properties of MRF, only selected sets of uncertainties are studied, and variations in the operating conditions can affect estimated quality of RDF.

Targeting cerebral diseases with enhanced delivery of therapeutic proteins across the blood-brain barrier

ABSTRACT Introduction Cerebral diseases have been threatening public physical and psychological health in the recent years. With the existence of the blood-brain barrier (BBB), it is particularly hard for therapeutic proteins like peptides, enzymes, antibodies, etc. to enter the central nervous system (CNS) and function in diagnosis and treatment in cerebral diseases. Fortunately, the past decade has witnessed some emerging strategies of delivering macromolecular therapeutic proteins across the BBB. Areas covered Based on the structure, functions, and substances transport mechanisms, various enhanced delivery strategies of therapeutic proteins were reviewed, categorized by molecule-mediated delivery strategies, carrier-mediated delivery strategies, and other delivery strategies. Expert opinion As for molecule-mediated delivery strategies, development of genetic engineering technology, optimization of protein expression and purification techniques, and mature of quality control systems all help to realize large-scale production of recombinant antibodies, making it possible to apply to the clinical practice. In terms of carrier-mediated delivery strategies and others, although nano-carriers/adeno-associated virus (AAV) are also promising candidates for delivering therapeutic proteins or genes across the BBB, some issues still remain to be further investigated, including safety concerns related to applied materials, large-scale production costs, quality control standards, combination therapies with auxiliary delivery strategies like focused ultrasound, etc.

Abstract 2088: gCNV-Seeker: A comprehensive germline CNV calling pipeline based on whole genome sequencing data

Abstract Germline Copy Number Variation (gCNV) is a type of genomic structural alteration including deletion or duplication of small genomic regions (50bp to 1MB) and can have an important role into cancer etiology. Whole genome sequencing (WGS) has been considered to be the most effective technology for genome-wide identification of gCNVs. However, an easy-to-use gCNV calling pipeline based on WGS data is still lacking. Here, we present the gCNV-Seeker, a user-friendly, rigorous computational pipeline to detect gCNV events based on WGS with standardized quality control and data visualization features. gCNV-Seeker initially adopts GATK probabilistic algorithms to detect a set of raw gCNV events and subsequently applies Binary Segmentation and Pruned Exact Linear Time (PELT) algorithms for re-segmentation and boundary revision of the gCNV candidates, respectively. In addition, gCNV-Seeker is built with several functionalities, including quality control, filtration, annotation and visualization to identify the gCNV regions (gCNVRs) of interest. We applied gCNV-Seeker to the WGS data from 872 lung cancers in never smokers from the Sherlock-Lung study and 3202 WGS data from the 1000 Genomes Project (1KGP) (reference) and identified CNVRs associated with lung cancer risk in never smokers. For example, in comparison to WGS data from 1KGP, we identified several CNVR candidates overlapping with known LC susceptible genes, e.g., the GSTM1/2 homozygous deletion (OR = 1.64, 95% CI=1.43-1.88, P < 0.01) and CYP2A6/7 homozygous or heterozygous deletion (OR = 1.59, 95% CI=1.24-2.03, P < 0.01). To evaluate its performance, we also carried out a comprehensive comparison of gCNV calling results between gCNV-Seeker and the 1KGP structural variant calling pipelines (PMID: 36055201) for common gCNVRs in the 1KGP WGS data. gCNV-Seeker showed a significant improvement on specificity and sensitivity for gCNVR detection compared with the 1KGP pipeline. In terms of specificity, 1315 out of 2692 (HGSV_9692) GSTM1/2 heterozygous deletion events (48.85%) originally identified by 1KGP were detected as homozygous deletions by gCNV-Seeker. These results were further confirmed by manual check. In terms of sensitivity, gCNV-Seeker detected total 299 deletion events in CYP2A6/7 regions, which were also manually confirmed. This corresponds to an increase of 48.02% compared to the 202 deletion events (HGSV_232739 & HGSV_232740) originally identified by the 1KGP pipeline. gCNV-Seeker will be a publicly available cross-platform (Linux and IOS) pipeline accessible in GitHub. Citation Format: Jian Sang, Tongwu Zhang, David Wedge, Maria Teresa Landi. gCNV-Seeker: A comprehensive germline CNV calling pipeline based on whole genome sequencing data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2088.

Abstract 252: A single-tube approach for detection of circulating tumor DNA using customized panels

Abstract Circulating tumor DNA (ctDNA) is a promising biomarker for cancer. Applications of ctDNA analysis include screening, diagnosis, treatment selection, minimal residual disease (MRD) detection and recurrence monitoring. While some applications are best served by tumor-agnostic panels covering large regions of the genome, such large panels are not universally appropriate due to limitations in sensitivity, user-friendliness, turn-around time (TAT), and sequencing cost. One application where customized, tumor-informed panels can be preferable is detection of MRD and cancer recurrence, and multiple studies have shown that ctDNA can detect residual/recurrent disease several months earlier than routine clinical imaging. This application requires high sensitivity and in most cases will involve repeat testing of longitudinal samples collected over several months or years. In this scenario, the ideal assay characteristics include tumor-informed, personalized assay panels, with a simple, rapid workflow, and with minimal cost per assay. We have developed the Fluent LBx assay to meet these requirements. Fluent LBx analysis can be performed on-site in any appropriately equipped research or clinical laboratory, avoiding the extra cost and delay associated with external testing. Fluent LBx is a variation on SiMSen-Seq (PMID 27060140) that uses modified target and adapter primer sequences to facilitate barcoding and uniform amplification of multiple targets in a single-tube library construction protocol. Library preparation can be completed in under 1.5 hours with approximately 20 minutes of hands-on time. Using this approach, target DNA molecules are first barcoded and then amplified with indexed adaptors compatible with Illumina sequencers, in a single PCR reaction. After clean-up and sequencing, barcode information is used to compile reads from individual DNA molecules and minimize base calling errors introduced during PCR and sequencing. Here we present data demonstrating uniformity, sensitivity and specificity of Fluent LBx assays using LGC SeraCare quality control standards. Additionally, we present longitudinal clinical demonstration of residual disease detection from ctDNA collected from multiple head and neck and gastrointestinal cancer patients through longitudinal monitoring post therapeutic intervention. The Fluent LBx workflow allows rapid, inexpensive, patient-specific monitoring of MRD and recurrence in multiple cancer indications. Citation Format: Robert Meltzer, Jessalyn Kaur, Ekaterina Kintsurashvili, Christopher D'Amato, Tony Godfrey. A single-tube approach for detection of circulating tumor DNA using customized panels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 252.

Abstract 3050: Quality control samples for future population-based microbiome studies

Abstract Introduction: There is a critical need for complex microbiome quality control standards representing population-based samples for microbial community profiling and analysis in large scale epidemiologic studies. Methods: We developed standard quality control samples from five volunteers with different phenotypes, comprising one obese female, one healthy male, one male on a low-carb diet, one infant, and one male with Crohn’s Disease, and evaluated their microbial metagenomic profiles within three laboratories at two different timepoints. To quantify the percentage of microbiome variability explained by donors, laboratory and sequencing run, a distance-based coefficient of determination R2 was estimated using a permutational multivariate analysis of variance. In addition, we calculated the intraclass correlation coefficients (ICC) for the relative abundance of the most abundant species, two alpha diversity metrics (i.e., observed number of species and Shannon index) and the first principal coordinates of three beta diversity matrices (i.e., Bray-Curtis, Jaccard and Aitchison) to estimate the accuracy of fecal microbial profiles between the three different laboratories as well as within the laboratories. Results: The variability introduced by the phenotype of the donors explained 82.7% to 95.3% of the overall variability, which was higher than the variability introduced by the laboratories (1.8% to 3.1%) and the sequencing runs (0.6% to 1.7%) - the residual percent variance explained varied between 2.2% and 12.4%. Observations based on principal coordinates analysis showed that samples clustered by donor and not by laboratory or sequencing runs. The five donor clusters were well separated and very distinct. Based on the comparison of species relative abundances, each donor displayed very different microbial profiles; and the microbial profiles of each donor were comparable between the three different laboratories and the two sequencing runs in each laboratory. The reproducibility within and between the laboratories was good to excellent for most diversity metrics (ICCs higher than 0.97) and species relative abundances (range, ICCs=0.70-0.99); however, the reproducibility of the observed number of species was moderate (ICC=0.64 for the first laboratory, ICC=0.78 for the second laboratory, ICC=0.81 for the third laboratory, and ICC=0.42 between the laboratories). Conclusions: These standard quality control samples can be used as a reference in future population-based epidemiologic studies to pool or meta-analyze microbiome data. Citation Format: Semi Zouiouich, Smriti Karwa, Yunhu Wan, Andrew Chan, Joseph Petrosino, Emma Allen-Vercoe, Rob Knight, Jianxin Shi, Mitchell Gail, Christian Abnet, Emily Vogtmann, Rashmi Sinha. Quality control samples for future population-based microbiome studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3050.