Leveraging Fecal Bacterial Survey Data to Predict Colorectal Tumors

Colorectal cancer (CRC) ranks second in cancer-associated mortality and third in the incidence worldwide. Most of CRC follow adenoma-carcinoma sequence, and have more than 90% chance of survival if diagnosed at early stage. But the recommended screening by colonoscopy is invasive, expensive, and poorly adhered to. Recently, several studies reported that the fecal bacteria might provide non-invasive biomarkers for CRC and precancerous tumors. Therefore, we collected and uniformly re-analyzed these published fecal 16S rDNA sequencing datasets to verify the association and identify biomarkers to classify and predict colorectal tumors by random forest method. A total of 1674 samples (330 CRC, 357 advanced adenoma, 141 adenoma, and 846 control) from 7 studies were analyzed in this study. By random effects model and fixed effects model, we observed significant differences in alpha-diversity and beta-diversity between individuals with CRC and the normal colon, but not between adenoma and the normal. We identified various bacterial genera with significant odds ratios for colorectal tumors at different stages. Through building random forest model with 10-fold cross-validation as well as new test datasets, we classified individuals with CRC, advanced adenoma, adenoma and normal colon. All approaches obtained comparable performance at entire OTU level, entire genus level, and the common genus level as measured using AUC. When combined all samples, the AUC of random forest model based on 12 common genera reached 0.846 for CRC, although the predication performed poorly for advance adenoma and adenoma

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling

BACKGROUND: It is one of the ultimate goals for modern biological research to fully elucidate the intricate interplays and the regulations of the molecular determinants that propel and characterize the progression of versatile life phenomena, to name a few, cell cycling, developmental biology, aging, and the progressive and recurrent pathogenesis of complex diseases. The vast amount of large-scale and genome-wide time-resolved data is becoming increasing available, which provides the golden opportunity to unravel the challenging reverse-engineering problem of time-delayed gene regulatory networks. RESULTS: In particular, this methodological paper aims to reconstruct regulatory networks from temporal gene expression data by using delayed correlations between genes, i.e., pairwise overlaps of expression levels shifted in time relative each other. We have thus developed a novel model-free computational toolbox termed TdGRN (Time-delayed Gene Regulatory Network) to address the underlying regulations of genes that can span any unit(s) of time intervals. This bioinformatics toolbox has provided a unified approach to uncovering time trends of gene regulations through decision analysis of the newly designed time-delayed gene expression matrix. We have applied the proposed method to yeast cell cycling and human HeLa cell cycling and have discovered most of the underlying time-delayed regulations that are supported by multiple lines of experimental evidence and that are remarkably consistent with the current knowledge on phase characteristics for the cell cyclings. CONCLUSION: We established a usable and powerful model-free approach to dissecting high-order dynamic trends of gene-gene interactions. We have carefully validated the proposed algorithm by applying it to two publicly available cell cycling datasets. In addition to uncovering the time trends of gene regulations for cell cycling, this unified approach can also be used to study the complex gene regulations related to the development, aging and progressive pathogenesis of a complex disease where potential dependences between different experiment units might occurs

How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study

Abstract Background Fecal microbiota transplantation (FMT) is reportedly the most effective therapy for relapsing Clostridium Difficile infection (CDI) and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians’ perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation. Methods A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed. Results Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians (33%) was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT (51.6% vs 27.8%, p = 0.021).More than half of the respondents (56.1%) were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem. Conclusions We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT

Effects of pantothenic acid on growth performance, slaughter performance, lipid metabolism, and antioxidant function of Wulong geese aged one to four weeks

This experiment was conducted to study the effects of pantothenic acid on the growth performance, slaughter performance, lipid metabolism, and antioxidant function of one-to four-week-old Wulong geese and determine the appropriate supplemental level of pantothenic acid. A total of 360 one-day-old Wulong geese were randomly divided into 6 groups with 6 replicates per group and 10 geese (5 males and 5 females) per replicate. The geese in group Ⅰ (control group) were fed a basal diet, and the geese in groups Ⅱ to Ⅵ (experimental groups) were given the basal diet supplemented with 8, 15, 30, 60, and 120 mg/kg pantothenic acid, respectively. The experiment lasted for 4 weeks. Based on the results of unrelated comparative analysis, the body weight was the highest when the dietary pantothenic acid level was 27.57 mg/kg. When the dietary pantothenic acid level was 26.17 mg/kg, the average daily gain peaked. When the dietary pantothenic acid level was 15.50 mg/kg, the feed:gain ratio was the lowest. The percentage of abdominal fat in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ (P < 0.05). The content of total cholesterol in serum in groups Ⅲ to Ⅴ was significantly lower than that in group Ⅰ (P < 0.05). The triglyceride content in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ (P < 0.01). The high-density lipoprotein–cholesterol content in group Ⅳ was significantly higher than that in group Ⅰ (P < 0.05). The total antioxidant capacity of serum and liver in group Ⅳ was significantly higher than that in group Ⅰ (P < 0.05). The malondialdehyde content in the liver in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ (P < 0.05). Glutathione peroxidase activity in the serum in group Ⅳ was significantly higher than that in group Ⅰ (P < 0.05). Glutathione peroxidase activity in the liver in groups Ⅳ and Ⅴ was significantly higher than that in group Ⅰ (P < 0.01). The addition of pantothenic acid in the diet of one-to four-week-old Wulong geese significantly affected the growth performance, slaughter performance, lipid metabolism, and antioxidant function of the geese. In terms of economic benefits, the optimal supplemental level of pantothenic acid in one-to four-week-old geese was 15.50 mg/kg

Gut Microbiota Characteristics of People with Obesity by Meta-Analysis of Existing Datasets

Obesity is a complex chronic, relapsing, progressive disease. Association studies have linked microbiome alterations with obesity and overweight. However, the results are not always consistent. An integrated analysis of 4282 fecal samples (2236 control (normal weight) group, 1152 overweight, and 894 simple obesity) was performed to identify obesity-associated microbial markers. Based on a random effects model and a fixed effects model, we calculated the odds ratios of the metrics, including bacterial alpha-diversity, beta-diversity, Bacteroidetes/Firmicutes ratio, common genera, and common pathways, between the simple obesity and control groups as well as the overweight and control groups. The random forest model was trained based on a single dataset at the genus level. Feature selection based on feature importance ranked by mean decrease accuracy and leave-one-out cross-validation was conducted to improve the predictive performance of the models. Chao1 and evenness possessed significant ORs higher than 1.0 between the obesity and control groups. Significant bacterial community differences were observed between the simple obesity and the control. The ratio of Bacteroidetes/Firmicutes was significantly higher in simple obesity patients. The relative abundance of Lachnoclostridium and Faecalitalea were higher in people with simple obesity, while 23 genera, including Christensenellaceae_R-7_group, Akkermansia, Alistipes, and Butyricimonas, etc., were significantly lower. The random forest model achieved a high accuracy (AUC = 0.83). The adenine and adenosine salvage pathway (PWY-6609) and the L-histidine degradation I pathway (HISDEG-PWY) were clustered in obese patients, while amino acid biosynthesis and degradation pathways (HISDEG-PWY, DAPLYSINESYN-PWY) were decreased. This study identified obesity microbial biomarkers, providing fertile targets for the management of obesity

Efficacy and safety of fecal microbiota transplantation in the treatment of ulcerative colitis: a systematic review and meta-analysis

Abstract To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates

Additional file 1: of How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study

Questionnaire: clinician's attitudes and perceptions of ethical and social issues in fecal microbiota transplantation. (DOCX 27 kb

Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling-1

<p><b>Copyright information:</b></p><p>Taken from "Discovery of time-delayed gene regulatory networks based on temporal gene expression profiling"</p><p>BMC Bioinformatics 2006;7():26-26.</p><p>Published online 18 Jan 2006</p><p>PMCID:PMC1386718.</p><p>Copyright © 2006 Li et al; licensee BioMed Central Ltd.</p>gnitude of mRNA expression ratio for each gene is represented by different colours. Red indicates mRNA abundance; green indicates a dearth; and gray indicates absence of the data. On the top bar(s), S phase and the time of mitoses (the arrows) are indicated, which was estimated by flow cytometry and BrdU (bromodeoxyuridine) labeling previously