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Biomedical subjects

Tao Chen

Publications and source records attributed to Tao Chen.

At least 19 recordsLinked to original sources

Exploring trop-2-directed ADCs monotherapy and combination therapy in pretreated mTNBC: a real-world study.

PURPOSE: Although Trop-2 antibody-drug conjugates (ADCs) have improved outcomes in pretreated metastatic triple-negative breast cancer (mTNBC), resistance remains common and the optimal combination strategy in routine practice is unclear. METHODS: In this retrospective real-world study, we identified patients with mTNBC from a health record-derived database who received sacituzumab govitecan or sacituzumab tirumotecan in the later-line setting between April 2020 and December 2025. Patients received at least two cycles of Trop-2 ADC therapy as monotherapy, plus a PD-1 inhibitor (dual-agent combination), or plus a PD-1 inhibitor and an antiangiogenic agent (triple-agent combination). RESULTS: Descriptively, the ORR was 57.1% in the triple-agent combination group, 38.5% in the dual-agent combination group, and 31.7% in the monotherapy group. Median follow-up was 15.2 months (95% CI, 8.7-20.6). Median progression-free survival (mPFS) was 15.4 months (95% CI, 5.3-NA) in the triple-agent combination group, 10.0 months (95% CI, 4.2-NA) in the dual-agent combination group, and 3.8 months (95% CI, 3.2-5.2) in the monotherapy group. Severe treatment-related toxicity was not increased in the combination groups. Exploratory analyses identified a genomic scoring system that may enable stratification of patients with a higher likelihood of benefiting from the triple-agent combination. CONCLUSION: To our knowledge, this study represents one of the earliest real-world evaluations of this triple-agent strategy in previously treated mTNBC, providing a basis for further prospective validation and biomarker-guided application.

Humans↗

Astigmatic vector outcomes after FS-LASIK versus SMILE for high myopic astigmatism: a single-center retrospective comparative cohort study without cyclotorsion compensation.

PURPOSE: To compare astigmatic correction vector outcomes between femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE, also termed Keratorefractive Lenticule Extraction, KLEx) without intraoperative cyclotorsion compensation in patients with high myopic astigmatism (-&#x2009;2.00 to&#x2009;-&#x2009;3.75 D), and to clarify procedure-specific correction tendencies under this non-standardized alignment protocol. METHODS: This single-center retrospective comparative cohort study enrolled 155 eyes (one eye randomly selected per patient) that underwent FS-LASIK (80 eyes) or SMILE/KLEx (75 eyes) for high myopic astigmatism correction from January 2023 to July 2024 in Beijing Fenglian Jiayue Lige Clinic. Intraoperative cyclotorsion compensation was intentionally disabled to isolate inherent procedural astigmatism correction characteristics. Standardized Alpins vectorial analysis was performed at 3&#xa0;months and 12&#xa0;months postoperatively. PRIMARY ENDPOINT: 12-month Alpins correction index (CI). Multivariable propensity score adjustment was applied to mitigate confounding by clinical treatment selection bias. Statistical multiplicity control was implemented for secondary vector and visual outcomes. RESULTS: Baseline demographic, refractive, corneal and ocular biometric parameters were balanced between groups after propensity matching. No statistically significant intergroup differences were detected in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual cylinder, safety index or efficacy index at 3 and 12&#xa0;months (all P&#x2009;>&#x2009;0.05). Under the non-cyclotorsion-compensated protocol, significant intergroup differences were identified in the magnitude of surgically induced astigmatism (SIA), correction index (CI), and magnitude error (ME) at both follow-up timepoints (all P&#x2009;<&#x2009;0.0001). Target induced astigmatism (TIA), difference vector (DV), index of success (IOS), and angle error (AE) magnitudes were comparable between groups (all P&#x2009;>&#x2009;0.05). The vector mean axis of DV differed significantly between groups at 3 and 12&#xa0;months (Watson-Williams circular test, all P&#x2009;<&#x2009;0.0001). No reoperations were documented in clinic medical records for either cohort. No standardized dry eye questionnaires, tear film testing or corneal nerve density metrics were collected to quantify dry eye adverse events; only unstructured clinical notes were reviewed for complication screening. CONCLUSIONS: Under surgical alignment without cyclotorsion compensation, FS-LASIK and SMILE/KLEx both yielded acceptable visual and refractive safety/efficacy for high myopic astigmatism (-&#x2009;2.00 to&#x2009;-&#x2009;3.75 D) at 1-year follow-up, but demonstrated divergent astigmatism correction tendencies: FS-LASIK exhibited relative astigmatism overcorrection (vector mean DV:&#x2009;-&#x2009;0.35&#x2009;&#xb1;&#x2009;0.43 D&#x2009;&#xd7;&#x2009;91&#xb0;, CI&#x2009;>&#x2009;1), while SMILE/KLEx showed relative undercorrection (vector mean DV:&#x2009;-&#x2009;0.21&#x2009;&#xb1;&#x2009;0.53 D&#x2009;&#xd7;&#x2009;12&#xb0;, CI&#x2009;<&#x2009;1). These correction biases are specific to the study's manual limbal alignment protocol without cyclotorsion tracking and cannot be generalized to modern optimized surgical platforms equipped with automated cyclotorsion compensation. Residual refractive errors across both groups are likely multifactorial, including differential corneal stromal healing responses, divergent femtosecond/excimer laser tissue modification mechanisms, and uncorrected intraoperative ocular cyclotorsion.

Humans↗

Safety and Stability of a Combined C2 Screw Placement Strategy With Vertebral Artery Mobilization.

BACKGROUND: Although C2 pedicle screws are considered the gold standard for atlantoaxial fixation, the optimal fixation strategy for patients with high-riding vertebral arteries (HRVA) or narrow C2 pedicles (NC2P) remains controversial because of the increased risk of vertebral artery injury and the limitations of alternative fixation techniques. OBJECTIVE: To evaluate the safety, stability, and clinical efficacy of an individualized C2 screw fixation strategy incorporating vertebral artery mobilization for complex upper cervical anatomy. METHODS: A retrospective study was conducted in 312 patients who underwent C2 fixation between 2017 and 2025. Patients were categorized according to fusion method, screw laterality, and VA transposition requirement. Bone fusion rates and screw accuracy (Gertzbein-Robbins grading) were compared across groups using &#x3c7;2, Fisher's exact, and multivariate logistic regression analyses to control confounders. RESULTS: All procedures were successfully completed without permanent neurovascular injury. At 6&#x2009;months, the fusion rate with an atlantoaxial fusion cage was significantly higher than with interlaminar bone grafting (92.3% vs. 51.0%, p&#x2009;<&#x2009;0.001). Unilateral C2 pedicle screw fixation combined with a contralateral alternative screw achieved comparable stability to bilateral fixation (p&#x2009;>&#x2009;0.05). Screw placement accuracy was 100% clinically acceptable in normal anatomy and 60% in cases requiring VA mobilization, with no VA injury or blood flow compromise. CONCLUSION: The proposed multi-strategy C2 screw placement protocol-integrating fusion cage support and VA mobilization-achieves superior fusion, reliable fixation, and high safety, even in anatomically challenging conditions. This approach provides a reproducible and versatile solution for C2 instrumentation in complex craniovertebral junction surgery.

Humans↗

Effects of aerobic exercise on inflammation and gut microbiota in obese mice: a metagenomic and metabolomic analysis.

BACKGROUND: Aerobic exercise can ameliorate insulin resistance (IR). However, the mechanism by which aerobic exercise regulates the gut microbiome to ameliorate IR and obesity remains unexplored. METHODS: Obese models were established by feeding C57BL/6 male mice a high-fat diet. A total of 26 mice were randomly divided into control group (group A, N&#x2009;=&#x2009;8) and high-fat diet group (HFD group, N&#x2009;=&#x2009;18). Successfully modeled mice were further assigned to model group (group B, N&#x2009;=&#x2009;8) and exercise group (group C, N&#x2009;=&#x2009;8). Group C underwent a 6-week treadmill exercise program (12&#xa0;m/min, 60&#xa0;min per day, 5 days per week). After intervention, colon tissue morphology was observed through hematoxylin-eosin staining, serum lipids and inflammatory indicators levels were detected by ELISA. The changes in the intestinal microbiota of the mice were also examined using metagenomic sequencing and UPLC-MS non-targeted metabolomics. RESULTS: Compared with the group A, the body weight, TC, TG, LDL-C, blood glucose, insulin, and IR in the group B significantly increased (P&#x2009;<&#x2009;0.01), while the levels of pro-inflammatory cytokines TXNIP, TNF-&#x3b1;, NLRP3, IL-1&#x3b2;, and IL-18 significantly increased (P&#x2009;<&#x2009;0.05 or P&#x2009;<&#x2009;0.01). Compared with the group B, aerobic exercise reduced the body weight, TC, blood glucose, insulin, IR, TXNIP, TNF-&#x3b1; and other indicators in obese mice (P&#x2009;<&#x2009;0.05 or P&#x2009;<&#x2009;0.01). Moreover, aerobic exercise can regulate the imbalance of the intestinal flora in obese mice and ameliorate the disorder of metabolites. The metabolic pathways including arachidonic acid metabolism and histidine metabolism showed the most significant differences after the intervention of aerobic exercise. CONCLUSIONS: In conclusion, aerobic exercise can ameliorate glucose and lipid metabolism, IR, inflammatory response, and regulate the intestinal microecology and metabolic disorders in obese mice. The mechanism may be closely related to enhancing the diversity of intestinal flora, regulating the metabolism of arachidonic acid and histidine.

Animals↗

Health-associated key gut microbiota drives the variation in community metabolic interactions in non-human primates.

Gut microbiota often undergo metabolic cross-feeding and resource competition. However, our understanding of global variations in these interactions and their implications for host health remain elusive. By analyzing a microbial genome catalog from 841 fecal metagenomes across 53 primate species worldwide, we identified key microbiota assigned to two taxa, i.e., Bacillota_A and Pseudomonadota, which well predicted the trade-off of community-level interaction types between metabolic competition and cooperation. Specifically, Bacillota_A species were inherently competitive and amino acid auxotrophic and typically found in anaerobic habitats. In contrast, members of Pseudomonadota were inherently cooperative, siderophore producers, and more abundant in aerobic conditions. Random forest models successfully distinguished unhealthy gut samples from healthy samples through the key competitive and cooperative microbiota, suggesting potential links between community metabolic interactions and host health. Together, this study enhances our mechanistic understanding of microbial interaction dynamism within complex gut ecosystems, offering new targets for understanding host health.

Animals↗

Evanescent imaging with induced polarization by using a solid immersion lens.

Image contrast enhancement, high lateral resolution, and height information are obtained with induced polarization evanescent imaging using a solid immersion lens. Experiments are conducted by imaging features on a patterned Si substrate. Imaging theory is used to predict optimum orientation of high-spatial-frequency samples, and a topographical image is derived from the induced polarization image through a calibration procedure. A numerical aperture of 1.5 is used in the experiment. Height accuracy of +/-2 nm is demonstrated with a known sample.

Journal Article↗

Selective expression of Bhlhb5 in subsets of early-born interneurons and late-born association neurons in the spinal cord.

Accumulating evidence has suggested that the basic helix-loop-helix transcription factors play important roles in controlling neuronal fate specification and differentiation in the developing central nervous system. In this study, we report a detailed immunological study on the expression of Bhlhb5 in embryonic mouse spinal cord with a newly developed antibody. At the early stage of neural development, Bhlhb5 is specifically expressed in dI6 dorsal interneurons and in V1 and V2 ventral interneurons. At late stages of development, Bhlhb5 expression is detected in a subset of late-born dorsal association interneurons that migrate into the uppermost layer of the dorsal horn.

Animals↗

Enhancement of riboflavin production by overexpression of acetolactate synthase in a pta mutant of Bacillus subtilis.

Genetic alterations of carbon flux into the acetoin biosynthesis pathway as a possible means to reduce acid accumulation were investigated in the riboflavin-producing Bacillus subtilis during growth on glucose. The lower rates of cell growth and riboflavin production were found in the pta-disrupted mutant while the rate of acetate formation was reduced. In contrast, acid accumulation was significantly reduced, to one-fifth that of the parental strain RH33::[pRB63](n), and a 50% increase in the riboflavin yield was obtained when the expression of the gene encoding acetolactate synthase was increased in the pta-disrupted mutant. Metabolic analysis, together with enzyme activity assays, indicated that the tricarboxylic acid cycle fluxes are significantly increased in response to acetolactate synthase overexpression in pta-disrupted mutant. Moreover, the intracellular ATP-to-ADP ratio also increased 5.8-fold. The high concentration of ATP could explain the increased riboflavin production.

Acetolactate Synthase↗

Time-resolved photoluminescence characteristics of subnanometer ZnO clusters confined in the micropores of zeolites.

Subnanometric ZnO clusters confined in different micropore zeolites are studied by steady-state and nanosecond time-resolved photoluminescence (PL) spectroscopy. The microsecond-scale lifetime is observed at room temperature for ZnO clusters confined in zeolites, which is significantly different from that of macrocrystalline ZnO on the external surface of zeolites. The dependence of luminescence lifetime on the amount of ZnO in zeolites indicates that the electron-phonon interactions between the ZnO clusters and the zeolite host significantly affect the dynamic relaxation process of ZnO clusters. The long lifetime luminescence of ZnO clusters can be achieved by weakening the coupling of electronic transition to zeolites host phonons. The similar long-lived luminescence is obtained when dispersing ZnO clusters into the porous SiO2. It is suggested that encapsulating the semiconductor cluster in the porous support is a possible way to inhibit or to retard the electron-hole recombination.

Journal Article↗

IL-12 p35 silenced dendritic cells modulate immune responses by blocking IL-12 signaling through JAK-STAT pathway in T lymphocytes.

Dendritic cells (DC) constitute a complex system of uniquely specialized antigen-presenting cells (APC) that play crucial roles in the initiation and regulation of immune responses. Recent studies have demonstrated that DC silenced by siRNA IL-12 p35 showed tolerogenic capacity in vitro. However, their mechanism of action is not fully understood. In this study, IL-12p35 siRNA was chemically synthesized and transfected into DCs. A coculture of T cells and DCs was performed. After 30 min coculture, T cells were harvested and analyzed. We showed that the IL-12 p35 silenced DCs decreased IL-12-induced T cell responses through blocking tyrosine phosphorylation of JAK2, TYK2, STAT3, and STAT4 proteins in T cells. These results demonstrate IL-12 p35 silenced DCs modulate immune responses by blocking IL-12 signaling through JAK-STAT pathway in T cells.

Animals↗

Characterization of SERCA2b Ca2+-Mg2+ ATPase mRNA decay by nuclear proteins.

Gene expression is controlled at several levels including mRNA decay. Sarco/endoplasmic reticulum Ca2+-Mg2+-ATPase isoform 2b (SERCA2b) is central to Ca2+ signalling and homeostasis in several tissues. SERCA2b mRNA decay involves interactions between cis-acting elements in its 3'-region and trans-acting nuclear protein factors. In the presence of the protein factors, the synthetic capped and polyadenylated RNA fragment 2b1 (3444-3753) decays faster than other SERCA2b 3'-region fragments. Here we determined the minimum cis-acting destabilizing element in the decay and its interactions with the nuclear protein factors. The in vitro decay required ATP hydrolysis and Mg2+ but not Ca2+. The decay was directional from 3' to 5', and involved a novel 35b GC rich domain designated 2b1-4 corresponding to 3521-3555. The decay of 2b1 RNA was decreased by (a) competition with 2b1-4, (b) mutation of 2b1 to delete 2b1-4, and (c) depleting the extracts of destabilizing trans-acting factors using immobilized 2b1-4. To determine the minimal destabilizing elements 2b1-4 was divided into 7b domains A-E. Deleting AB, BC, CD or DE inactivated the destabilizing cis-acting element but deleting A, B, C, D or E had no effect. In electrophoresis mobility shift assays the nuclear protein extracts retarded the mobility of labeled uncapped 2b1 RNA without a poly A+ tail. A positive co-operativity in the interactions was shown in protein concentration dependence of the shift and in the competition of 2b1-4 in inhibiting the mobility of 2b1 RNA. Based on further experiments, the domain CDE (3535-3555) was sufficient to compete with 2b1 RNA for the protein binding. Consistent with this competition, excess CDE RNA retarded the in vitro decay of 2b1 RNA. Thus the RNA decay required ATP hydrolysis and Mg2+ but not Ca2+, the minimum binding domain was in the sequence 3535-3555, and the decay may involve a multimeric protein complex.

3' Untranslated Regions↗

Micelle formation and drug release behavior of polypeptide graft copolymer and its mixture with polypeptide block copolymer.

Self-association behavior of polypeptide graft copolymer and its mixture with polypeptide block copolymer and drug carrier capability of the formed micelles was examined. The results gained through fluorescence spectroscopy, transmission electron microscopy and nuclear magnetic resonance spectroscopy revealed that both polypeptide graft copolymer and its mixture with polypeptide block copolymer can self-assemble to form polymeric micelles in aqueous media. The molecular structure of the graft copolymer and blending the graft with block copolymer exert marked effects on the critical micelle concentration and the shape of formed micelles. It was found that the hydrophobic inner core of the micelles formed either by graft copolymer or mixture of graft and block copolymers can act as an incorporation site for the hydrophobic drugs. The drug loading content of the graft copolymer micelles tends to be larger when the content of the polypeptide segments in the copolymer increases. The results obtained from the drug-release studies showed that the drug-release rates are dependent on the chemical nature of the graft copolymer, the composition of the graft and block copolymer mixture, and also the pH value of the release media.

Anti-Inflammatory Agents, Non-Steroidal↗

ACB-PCR measurement of K-ras codon 12 mutant fractions in livers of Big Blue rats treated with N-hydroxy-2-acetylaminofluorene.

K-ras codon 12 GGT-->GAT and GGT-->GTT mutations are the most frequently observed K-ras point mutations in human and rodent tumors and therefore are implicated in carcinogenesis for many tissues. Measurement of these mutations in rat models and human tissue could facilitate a more logical extrapolation of rodent tumorigenesis data to human disease. We have developed allele-specific competitive blocker PCR (ACB-PCR) assays for rat K-ras codon 12 GGT-->GTT and GGT-->GAT mutations that parallel the already published assays for human K-ras codon 12 mutations. Liver K-ras codon 12 mutant allele fractions were measured in vehicle-treated and N-hydroxy-2-acetylaminofluorene (N-OH-AAF)-treated Big Blue rats. The average K-ras codon 12 GGT-->GTT mutant fraction (MF) for four control rats was 50 x 10(-6) (95% CI: 27 x 10(-6), 95 x 10(-6)) and for four treated rats was 165 x 10(-6) (95% CI: 87 x 10(-6), 312 x 10(-6)), indicating a 3.3-fold increase with treatment (95% CI: 1.3-8.1). The average MF of K-ras codon 12 GGT-->GAT for control rats was 1320 x 10(-6) (95% CI: 498 x 10(-6), 3500 x 10(-6)) and for treated rats was 8450 x 10(-6) (95% CI: 3180 x 10(-6), 22 400 x 10(-6)), indicating a 6.4-fold increase with treatment (95% CI: 1.6-25.4). These transgenic rats were part of a study that included analysis of liver lacI mutations. Although data from lacI determinations show that this compound induces mostly G-->T mutations, using the ACB-PCR method both K-ras codon 12 GGT-->GTT and GGT-->GAT MFs were significantly increased in treated rats versus control rats. This data raises the possibility that N-OH-AAF may not only induce mutations by a genotoxic mechanism, but also by amplification of both de novo and pre-existing K-ras mutation.

Alleles↗

DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver.

Aristolochic acid (AA) is a potent nephrotoxin and carcinogen and is the causative factor for Chinese herb nephropathy. AA has been associated with the development of urothelial cancer in humans, and kidney and forestomach tumors in rodents. To investigate the molecular mechanisms responsible for the tumorigenicity of AA, we determined the DNA adduct formation and mutagenicity of AA in the liver (nontarget tissue) and kidney (target tissue) of Big Blue rats. Groups of six male rats were gavaged with 0, 0.1, 1.0 and 10.0 mg AA/kg body weight five times/week for 3 months. The rats were sacrificed 1 day after the final treatment, and the livers and kidneys were isolated. DNA adduct formation was analyzed by 32P-postlabeling and mutant frequency (MF) was determined using the lambda Select-cII Mutation Detection System. Three major adducts (7-[deoxyadenosin-N6-yl]-aristolactam I, 7-[deoxyadenosin-N6-yl]-aristolactam II and 7-[deoxyguanosin-N2-yl]-aristolactam I) were identified. There were strong linear dose-responses for AA-induced DNA adducts in treated rats, ranging from 25 to 1967 adducts/10(8) nucleotides in liver and 95-4598 adducts/10(8) nucleotides in kidney. A similar trend of dose-responses for mutation induction also was found, the MFs ranging from 37 to 666 x 10(-6) in liver compared with the MFs of 78-1319 x 10(-6) that we previously reported for the kidneys of AA-treated rats. Overall, kidneys had at least two-fold higher levels of DNA adducts and MF than livers. Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutation spectra in both kidney and liver of AA-treated and control rats, but there was no significant difference between the mutation spectra in AA-treated livers and kidneys. A:T-->T:A transversion was the predominant mutation in AA-treated rats; whereas G:C-->A:T transition was the main type of mutation in control rats. These results indicate that the AA treatment that eventually results in kidney tumors in rats also results in significant increases in DNA adduct formation and cII MF in kidney. Although the same treatment does not produce tumors in rat liver, it does induce DNA adducts and mutations in this tissue, albeit at lower levels than in kidney.

Animals↗

Analysis of gene expression changes in relation to toxicity and tumorigenesis in the livers of Big Blue transgenic rats fed comfrey (Symphytum officinale).

BACKGROUND: Comfrey is consumed by humans as a vegetable and a tea, and has been used as an herbal medicine for more than 2000 years. Comfrey, however, is hepatotoxic in livestock and humans and carcinogenic in experimental animals. Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in rat liver. RESULTS: In this study, we identified comfrey-induced gene expression profile in the livers of rats. Groups of 6 male transgenic Big Blue rats were fed a basal diet and a diet containing 8% comfrey roots, a dose that resulted in liver tumors in a previous carcinogenicity bioassay. The animals were treated for 12 weeks and sacrificed one day after the final treatment. We used a rat microarray containing 26,857 genes to perform genome-wide gene expression studies. Dietary comfrey resulted in marked changes in liver gene expression, as well as in significant decreases in the body weight and increases in liver mutant frequency. When a two-fold cutoff value and a P-value less than 0.01 were selected, 2,726 genes were identified as differentially expressed in comfrey-fed rats compared to control animals. Among these genes, there were 1,617 genes associated by Ingenuity Pathway Analysis with particular functions, and the differentially expressed genes in comfrey-fed rat livers were involved in metabolism, injury of endothelial cells, and liver injury and abnormalities, including liver fibrosis and cancer development. CONCLUSION: The gene expression profile provides us a better understanding of underlying mechanisms for comfrey-induced hepatic toxicity. Integration of gene expression changes with known pathological changes can be used to formulate a mechanistic scheme for comfrey-induced liver toxicity and tumorigenesis.

Animal Feed↗

Gene expression profiles distinguish the carcinogenic effects of aristolochic acid in target (kidney) and non-target (liver) tissues in rats.

BACKGROUND: Aristolochic acid (AA) is the active component of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. AA, however, induced nephropathy and urothelial cancer in people and malignant tumors in the kidney and urinary tract of rodents. Although AA is bioactivated in both kidney and liver, it only induces tumors in kidney. To evaluate whether microarray analysis can be used for distinguishing the tissue-specific carcinogenicity of AA, we examined gene expression profiles in kidney and liver of rats treated with carcinogenic doses of AA. RESULTS: Microarray analysis was performed using the Rat Genome Survey Microarray and data analysis was carried out within ArrayTrack software. Principal components analysis and hierarchical cluster analysis of the expression profiles showed that samples were grouped together according to the tissues and treatments. The gene expression profiles were significantly altered by AA treatment in both kidney and liver (p < 0.01; fold change > 1.5). Functional analysis with Ingenuity Pathways Analysis showed that there were many more significantly altered genes involved in cancer-related pathways in kidney than in liver. Also, analysis with Gene Ontology for Functional Analysis (GOFFA) software indicated that the biological processes related to defense response apoptosis and immune response were significantly altered by AA exposure in kidney, but not in liver. CONCLUSION: Our results suggest that microarray analysis is a useful tool for detecting AA exposure; that analysis of the gene expression profiles can define the differential responses to toxicity and carcinogenicity of AA from kidney and liver; and that significant alteration of genes associated with defense response, apoptosis and immune response in kidney, but not in liver, may be responsible for the tissue-specific toxicity and carcinogenicity of AA.

Animals↗

GOFFA: gene ontology for functional analysis--a FDA gene ontology tool for analysis of genomic and proteomic data.

BACKGROUND: Gene Ontology (GO) characterizes and categorizes the functions of genes and their products according to biological processes, molecular functions and cellular components, facilitating interpretation of data from high-throughput genomics and proteomics technologies. The most effective use of GO information is achieved when its rich and hierarchical complexity is retained and the information is distilled to the biological functions that are most germane to the phenomenon being investigated. RESULTS: Here we present a FDA GO tool named Gene Ontology for Functional Analysis (GOFFA). GOFFA first ranks GO terms in the order of prevalence for a list of selected genes or proteins, and then it allows the user to interactively select GO terms according to their significance and specific biological complexity within the hierarchical structure. GOFFA provides five interactive functions (Tree view, Terms View, Genes View, GO Path and GO TreePrune) to analyze the GO data. Among the five functions, GO Path and GO TreePrune are unique. The GO Path simultaneously displays the ranks that order GOFFA Tree Paths based on statistical analysis. The GO TreePrune provides a visual display of a reduced GO term set based on a user's statistical cut-offs. Therefore, the GOFFA visual display can provide an intuitive depiction of the most likely relevant biological functions. CONCLUSION: With GOFFA, the user can dynamically interact with the GO data to interpret gene expression results in the context of biological plausibility, which can lead to new discoveries or identify new hypotheses. AVAILABILITY: GOFFA is available through ArrayTrack softwarehttp://edkb.fda.gov/webstart/arraytrack/.

Genomics↗