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PubMed2025

AI-HOPE: an AI-driven conversational agent for enhanced clinical and genomic data integration in precision medicine research.

MOTIVATION: The growing complexity of clinical cancer research has fueled a surge in demand for automated bioinformatics tools capable of integrating clinical and genomic data to accelerate discovery efforts. RESULTS: We present the Artificial Intelligence Agent for High-Optimization and Precision Medicine (AI-HOPE), an AI-driven system that enables domain experts to conduct integrative data analyses through natural language interactions. Powered by Large Language Models, AI-HOPE interprets user instructions, converts them into executable code, and autonomously analyzes locally stored data. It supports flexible association studies, subset comparisons, clinical prevalence assessments and survival analyses. In addition, AI-HOPE enables global variable scans to identify features significantly associated with a user-defined outcome, making a powerful and intuitive tool for advancing precision medicine research. Importantly, its closed-system design prevents clinical data leakage. To demonstrate its utility, AI-HOPE was applied to The Cancer Genome Atlas data to address two clinical questions. First, it identified significant enrichment of TP53 mutations in late-stage colorectal cancer compared to early-stage cases. Second, it uncovered a strong association between KRAS mutations and poorer progression-free survival in FOLFOX-treated patients. These findings align with established literature and demonstrate AI-HOPE's ability to generate meaningful insights independently, without prior assumptions. By removing programming barriers and simplifying complex analyses, AI-HOPE bridges the gap between data complexity and research needs. With its scalable and adaptable framework, AI-HOPE has the potential to support diverse biomedical research fields, driving innovation and efficiency in translational studies. AVAILABILITY AND IMPLEMENTATION: The AI-HOPE software and demonstration data is available at https://github.com/Velazquez-Villarreal-Lab/AI-HOPE.

Precision Medicine↗
PubMed1995

The relation between the PST1 restriction fragment length polymorphism at the APO-AI locus and plasma APO-AI concentrations in marathon runners.

A PST1 restriction fragment length polymorphism (RFLP), located close to the apolipoprotein AI (apo-AI) gene on chromosome 11, is associated with elevated levels of apo-AI in normal healthy individuals and with depressed levels in patients with coronary heart disease. In both cases the association is with the P2 allele (the allele not containing the PST1 cutting site). Prolonged exercise is known to increase steady-state plasma apo-AI concentrations. We investigated the effect of adaptation to endurance exercise on the association of the PST1 marker with plasma apo-AI levels. Eighty-two male subjects between the ages of 20 and 50 years were randomly selected from a group of local marathon runners. The frequency of the P2 allele was 14% in this group. This was similar to the frequency reported for this RFLP in other population groups of healthy men. Plasma levels of apo-AI were elevated in the marathon runners compared with randomly selected healthy South African men in the same age group. There was, however, no association between the PST1 RFLP and the plasma high-density lipoprotein cholesterol and/or apo-AI concentrations in this group. The elevated apo-AI levels in marathon runners therefore bear no relation to differences associated with the PST1 RFLP at the apo-AI gene locus.

Adaptation, Physiological↗
PubMed1990

G to A substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI and high density lipoprotein cholesterol concentrations.

We have determined the sequence of 250 bases 5' of the transcriptional start site of the apolipoprotein AI gene in a human individual with high serum concentrations of apo AI. One of the alleles contained a G to A substitution at position -75, between the CACAT sequence and the TAAATA box, creating a tandem repeat, CAGGGC-CA*GGGC. The substitution destroys an MspI cutting site, and the polymerase chain reaction and MspI digestion were used to identify the presence of the A or G base. The frequency of the A substitution in 96 healthy men from Bristol was 0.11 and this was increased to 0.25 in men with serum apo AI concentrations greater than 180 mg/dl. Men with the A allele had significantly higher serum concentrations of apo AI, high density lipoprotein (HDL) cholesterol and HDL2 than those with the G allele. In this sample, variation associated with the G to A substitution accounted for 6% and 4.6% of the total variance in apo AI and HDL cholesterol concentrations, respectively. Although there is as yet no functional proof, it is possible that the A substitution may be having a direct positive effect on the rate of apo AI gene transcription and thus be associated with increased apo AI and HDL cholesterol concentrations because of increased production of apo AI protein from the liver or intestine.

Alleles↗
PubMed1992

Polymorphisms in the apolipoprotein (apo) AI-CIII-AIV gene cluster: detection of genetic variation determining plasma apo AI, apo CIII and apo AIV concentrations.

We have examined the associations between levels of plasma apolipoprotein (apo) AI, apo CIII and apo AIV and genetic variation in the apo AI-CIII-AIV gene cluster in 162 boys and young men from Belgium aged from 7 to 23 years. Genotypes were determined for six restriction enzymes XmnI, PstI, SstI, PvuIIA-CIII, PvuIIB-AIV and XbaI, and for the G to A substitution at -75 bp in the 5' region of the apo AI gene. The polymorphism most strongly associated with apo AI levels was the G to A substitution (P = 0.025, R2 x 100 = 3.6%) confirming previous observations. The polymorphism most strongly associated with apo CIII levels was that of PvuIIA-CIII (P = 0.023, R2 x 100 = 2.9%) in the apo CIII gene. This novel association must be interpreted with caution until it has been confirmed in an independent sample. The polymorphism associated with the largest effect on apo AIV levels was that detected with XbaI in the apo AIV gene, but this association was not statistically significant. Previously reported associations between the SstI polymorphism and triglyceride levels, and between the PstI polymorphism and apo AI levels, were weakly detected in the present sample. Our results show that variation associated with some of the polymorphisms in the apo AI-CIII-AIV cluster makes a small, but statistically significant, contribution to the determination of apo AI and apo CIII levels in this sample of young men and boys. These observations may, in part, explain reported associations between polymorphisms in this gene cluster, differences in plasma lipid and lipoprotein levels, and prevalence of coronary artery disease.

Adolescent↗
PubMed1999

Use of AI technician scores for body condition, uterine tone and uterine discharge in a model with disease and milk production parameters to predict pregnancy risk at first AI in Holstein dairy cows.

Technicians recorded body condition score (BCS) and several parameters related to estrus and/or metritis for 1694 first insemination cows on 23 farms. Additional variables for modeling the adjusted odds ratios (OR) for pregnancy were data on disease prior to or within 21 days of AI and test day milk yields. Significant predictors for pregnancy were farm, year and season, BCS, uterine tone, contaminated insemination gun after AI, fat-protein corrected kilograms milk (FPCM), days in milk (DIM), and diseases. Vaginal mucus, ease of cervical passage, and lameness were not significant predictors for pregnancy. Pregnancy risk at AI increased with increasing DIM, reaching a near optimum after 82 days. Lack of uterine tone was associated with a lowered pregnancy risk (OR = 0.69) as was contaminated insemination gun (OR = 0.67), first-parity lactation, FPCM >33 kg (OR = 0.71), BCS 2.5 at AI (OR = 0.65), clinical mastitis (OR = 0.53), cystic ovarian disease (OR = 0.53), and metritis (OR = 0.74). It was concluded that data on BCS and uterine findings, as collected by AI technicians, are significant predictors of AI outcome. Dairy producers and veterinarians should jointly examine the potential costs and value of such AI technician-based data to improve herd fertility.

Animals↗
PubMed1987

Anemia-inducing substance (AIS) in advanced cancer: inhibitory effect of AIS on the function of erythrocytes and immunocompetent cells.

The effects of anemia-inducing substance (AIS), found in the plasma of tumor-bearing subjects, on red blood cells (RBC) and cellular immunity were examined. The results obtained may be summarized as follows: 1) The osmotic resistance and the deformability of RBC were decreased in patients with terminal cancer. 2) Normal human RBC were made less deformable and their membrane was made fragile by treatment with cachectic plasma from those patients, and these changes in physical properties were irreversible. 3) Energy metabolism in RBC was affected by AIS, that is, ATP concentration and pyruvate kinase activity in RBC were lowered and transmembrane glucose influx was suppressed. 4) AIS was removed from cachectic plasma by repeated adsorption with normal RBC, and the inhibitory effect on cellular immunity was lessened as AIS was removed. 5) AIS was detected in cachectic RBC membrane, monocytes, and tumor tissue by indirect immunofluorescence assay using rabbit anti-AIS antibody prepared by us. These observations suggest strongly that tumor-derived AIS appears in the blood of patients with terminal cancer, shows cytotoxicity to RBC and immunologically competent cells, and plays a role in the pathogenesis of cancer cachexy.

Adenosine Triphosphate↗
PubMed1994

Guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein AI gene is associated with elevated serum apolipoprotein AI levels in Chinese non-smokers.

The influence of the guanidine to adenine (G/A) substitution in the promoter region of the apolipoprotein (apo) AI gene (at -75 bp) on serum lipids and apolipoproteins was studied in 287 healthy Chinese of both sexes in Singapore. Women had significantly higher levels of high-density lipoprotein cholesterol (HDLC) and apo AI and lower low-density lipoprotein cholesterol (LDLC). The distribution of genotypes was at Hardy-Weinberg equilibrium. The frequency of the A allele in the Chinese was significantly higher [0.27; 95% confidence interval (CI) 0.24-0.31] than that reported in Caucasians (0.12; 95% CI 0.09-0.14). In men, the A allele was associated with 20% higher apo AI; this association was completely absent in women. Furthermore, in men this association was only observed in those who had never smoked, and was absent in smokers. The G/A substitution explained 9% (P < 0.02) of the sample variance of apo AI in non-smoking men. The modulating influence of smoking could not be examined in women because too few women smoke. Although the impact of this polymorphism is modulated by hormones and smoking, it is of importance in determining levels of apo AI in healthy Chinese individuals. No association of the G/A substitution of the apo AI gene was observed with any other lipid traits.

Adenine↗
PubMed2000

Androgen insensitivity syndrome (AIS): emotional reactions of parents and adult patients to the clinical diagnosis of AIS and its confirmation by androgen receptor gene mutation analysis.

The emotional reactions of parents and adult patients on disclosure of the clinical diagnosis of androgen insensitivity syndrome (AIS) and its later confirmation by gene mutation analysis were assessed. A semistructured interview and three questionnaires were used. Parents came from 18 different families with a total of 20 children (15 complete AIS, 5 partial AIS), 19 raised as girls, 1 as a boy. Ten adult women with complete AIS came from six families. The short-term reaction upon the clinical diagnosis was in the majority of both parents and adult patients associated with shock, grief, anger, and shame and in the mothers and adult patients with guilt. Emotional reactions were more long-lasting in mothers and adult patients than in fathers. The confirmation by DNA analysis did not alter the actual feelings of both parents. Adolescents with AIS should be informed completely - but in a step-by-step way - about their condition, since adult patients indicated that they had suffered from being not at all or misinformed about AIS in their adolescence.

Adult↗
PubMed1990

Visual projections induced into the auditory pathway of ferrets. I. Novel inputs to primary auditory cortex (AI) from the LP/pulvinar complex and the topography of the MGN-AI projection.

The organization of cortical circuitry responsible for processing sensory information is a subject of intense examination. However, it is not known whether cortical cells in different sensory cortices process information in a way that is specific to the modality of their input, or whether there are commonalities in processing circuitry across different cortices. In our laboratory, this question has been investigated at the level of the geniculocortical pathway by routing information of one sensory modality into the processing circuitry of another modality. Appropriate early lesions cause growth of retinal axons into the auditory thalamus (MGN) (Sur et al., Science 242:1437, '88). Previously, we have established that the MGN carries the resulting visual information on to primary auditory cortex (AI), which thus contains visually responsive neurons and a topographic representation of the retina (Roe et al., Soc. Neurosci. Abstr. 14:460, '88; Sur et al., Science 242:1437, '88). In this paper, we describe anomalous projections from the dorsal part of the thalamus, specifically the lateral posterior/pulvinar complex, into AI. This result demonstrates that thalamic neurons belonging to one modality can be induced to project to cortex that is normally of a different modality. In addition, we have studied in detail the nature of the MGN to AI projection in these animals as compared to the normal projection. The MGN to AI projection appears to be unaltered by the lesions; the location and topography of labelled cells are similar to that in normal animals. Because the MGN to AI projection is still highly divergent along the "isofrequency" dimension when compared to the tonotopic dimension, our data suggest that visual topography in the cortical map is created within the auditory cortex, perhaps by activity-dependent sharpening of the retinal representation during development.

Animals↗
PubMed1990

A comparison of AIS-85 with AIS-80 for injury scaling in blunt trauma.

As the effects on injury scaling of the differences between the 1980 and 1985 revisions of the AIS are unknown in blunt trauma, we compared them in all 1270 critically injured (median ISS, 26) blunt trauma patients (75% male, 74% road crash, overall mortality 17%) admitted to the Department of Critical Care Medicine at Auckland Hospital from 1983 through 1987. In 911 patients (72%) there were no differences between AIS-80 and AIS-85 in any body region or in derived ISS. Changes in AIS grades were most common in the abdomen (205 patients), thorax (100 patients), and head (61 patients) regions. Median ISS overall for the 1270 patients was unchanged at 26. One percent of patients had changes in ISS of 16-24 points. Direct comparison of groups of patients scored with these two revisions of the AIS is inappropriate, particularly in those with abdomen region injury.

Humans↗
PubMed1998

Linkage disequilibrium of the Apo AI-CIII-AIV gene cluster and their relationship to plasma triglyceride, apolipoprotein AI and CIII levels in Koreans.

More than 20 different RFLPs have been described in the apo AI-CIII-AVI gene cluster and their association with several dyslipidemias has been claimed in different populations. So far, however, the results of their association have been largely inconclusive. We analyzed six previously described RFLPs (Paul-Hayase et al., 1992) in the apo AI-CII-AIV gene cluster by using PCR-amplified DNAs in 132 healthy subjects to document the relationship between the RFLPs and dyslipoproteinemias. The polymorphic sites were located in the promoter region of the apo AI gene (G to A substitution, MspI), in the 3' flanking region of the apo AI gene (PstI), in the 3' noncoding region of the apo CIII gene (SstI), in the first intron of the apo CIII gene (PvuIIa), in the intergenic region of the apo CIII and apo AIV genes (PvuIIb), and in the second intron of the apo AIV gene (XbaI), respectively. The allele frequencies of PstI polymorphism showed no ethnic difference. However, in G to A substitution sites (MspI), Koreans had a lower G allele frequency than that of Caucasians. Among Oriental ethnic groups there were no significant differences in the allele frequencies of SstI and PvuIIa RFLPs, whereas significant differences existed between individuals of Oriental, Caucasian, and/or African origins. Koreans were monomorphic for PvuIIb and XbaI restriction sites. Pairwise linkage disequilibrium analysis revealed two pairs of significant negative linkage disequilibriums (MspI-SstI and SstI-PvuIIa). Although there were no statistical significances, the S2 allele of SstI polymorphism and the G allele of MspI polymorphism seemed to be associated with hypertriglyceridemia. Thus linkage of the G allele of MspI polymorphism and the S2 allele of SstI polymorphism could give an additive effect on an increment of triglyceride levels. We did not find any association between the SstI polymorphism and apo CIII levels. In conclusion, there were no statistically significant relationships detected between the apo AI-CIII-AVI gene cluster polymorphisms and the levels of various lipid parameters.

Adolescent↗
PubMed1984

Isolation and DNA sequence of full-length cDNA and of the entire gene for human apolipoprotein AI--discovery of a new genetic polymorphism in the apo AI gene.

We have isolated full-length cDNA clones for apolipoprotein AI from a human fetal liver cDNA library made in the vector lambda gt10. One such clone, pBL13AI, was 965 nucleotides long and contained the entire preproapolipoprotein AI sequence, in addition to 86 nucleotides of 5' untranslated region and 75 nucleotides of the 3' untranslated region. The complete structure of this clone is presented. Furthermore, we have obtained a 20-kb genomic fragment from a human genomic library, encompassing the entire apo AI gene. Sequence analysis of the gene shows that the coding region is interrupted by three introns of 197, 187, and 588 bp, respectively. Digestion of the DNA of various individuals with the endonuclease Msp I revealed a new restriction site polymorphism in the apo AI gene.

Apolipoprotein A-I↗
PubMed1990

Influence of dietary lipids on serum apoproteins AI and B and on intestinal synthesis of apo AI in the early weaning of piglets: comparison of saturated, unsaturated, and medium-chain triglycerides.

Early weaning of piglets induces a rapid decrease in the concentration of all plasma lipoproteins within 2 d. The decline was more progressive when 20% saturated fatty acid (lard) (SF) was added to the diet; saturated fatty acid was more effective than unsaturated fatty acid (sunflower oil) (UF). Medium-chain triglycerides had no protective effect. Intestinal synthesis of apoprotein AI was twofold higher in preweaning piglets than in adults (12.9% of total synthesis vs 5.9%, p less than 0.01) when measured in intestinal mucosa. On day 4 of weaning, synthesis was still at the preweaning level in all groups but on day 7 was maintained only by the SF diet (11.7%). We conclude that long-chain lipids, particularly saturated fatty acids, prevent a decrease in lipoproteins at weaning, mainly by maintaining intestinal apo AI synthesis at a high level.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Apolipoprotein AI- and AI:AII-containing lipoproteins in white men and women of the HERITAGE Family study: Associations with metabolic risk profile variables.

It is now well established that an increased high-density lipoprotein (HDL) cholesterol level, especially in the HDL(2) subfraction, is associated with a reduced risk of coronary heart disease (CHD). However, little is known about the associations between the apolipoprotein (apo) composition of HDL and CHD metabolic risk factors. In the present study, we examined the gender differences in plasma concentration of HDL containing apo AI only (LpAI) versus both apoAI and apoAII (LpAI/AII), and also compared their associations with body composition, adipose tissue (AT) distribution, and metabolic risk profile variables. For that purpose, we measured fasting plasma lipoprotein-lipid levels including LpAI and LpAI/AII concentrations in a sample of 215 men and 174 women, all Caucasians, of the HERITAGE Family Study. All subjects underwent anthropometric, body fatness (underwater weighing) and abdominal AT accumulation (computed tomography) measurements. We found that, women had higher LpAI and lower LpAI/AII concentrations compared with men. Whereas in women, LpAI levels were correlated to body fat mass and waist circumference, no association between body composition, fat distribution, and LpAI concentrations was noted in men. Increased LpAI concentrations were associated with higher HDL(2) cholesterol levels in both men and women. Overall, elevated LpAI and LpAI/AII concentrations showed contrasting associations with metabolic risk profile variables as high LpAI, but not LpAI/AII concentrations were associated with a more favorable metabolic risk profile. We also found that high HDL cholesterol appeared to be more closely related to a better metabolic risk profile than high LpAI in both genders. Our results suggest that LpAI and HDL cholesterol levels are good correlates of the metabolic profile, but that HDL cholesterol concentrations could still represent a better index in CHD risk assessment.

Adipose Tissue↗
PubMed2002

The effect of endurance exercise training on plasma lipoprotein AI and lipoprotein AI:AII concentrations in sedentary adults.

The effect of 6 months of endurance exercise training on plasma concentrations of lipoprotein (Lp)AI and LpAI:AII was determined in 39 sedentary subjects (17 men, 22 women, average age, 57 years) with abnormal cholesterol concentrations (total cholesterol [TC] > 200 mg/dL, or high-density lipoprotein-cholesterol [HDL-C] < 35 mg/dL). Following exercise training, plasma LpAI concentrations increased (+5.9 +/- 1.2 mg/dL; P <.001), but there was no change in total apolipoprotein (apo) A-I or LpAI:AII concentrations. The change in plasma LpAI concentration was positively correlated to changes in total HDL-C (r =.495, P =.001), the sum of HDL4-C(nmr) + HDL5-C(nmr) (r =.417, P =.008), and average HDL particle size (r =.415, P =.009), but not to changes in body composition or Vo2max. In the 8 subjects with the greatest change in LpAI concentration following training, the size distribution of LpAI and LpAI:AII particles in plasma also was measured before and after training. In these subjects, the size distribution of LpAI:AII particles did not change with training, but there was a significant increase (0.1 nm; P =.048) in the peak size of the "medium" (7.8 to 9.8 nm) LpAI particles after training. In 7 subjects who served as age- and weight-matched sedentary controls, plasma concentrations of total apo A-I, the LpAI and LpAI:AII subfractions, and plasma lipoprotein-lipids did not differ significantly between baseline and final testing. These data indicate that endurance exercise training increases the average size and plasma concentrations of LpAI, but not LpAI:AII, particles, which may represent possible enhancements of reverse cholesterol transport and may provide insight into the role that exercise plays in reducing cardiovascular disease risk.

Aged↗
PubMed2000

Interaction of alcohol and the G to a substitution at the promoter region of the apolipoprotein AI gene in determining plasma apolipoprotein AI levels in Yi and Han Chinese.

OBJECTIVE: To investigate the influence on plasma lipid levels of alcohol and a common polymorphism in the human apolipoprotein AI gene promoter at a position 75 bp upstream of the transcription start site. METHODS: For this study, 742 healthy Yi and Han subjects all above 15 years old formed the total population which was divided into three groups: the Yi-farmer group, the Yi-emigrant group and the Han-resident group. All estimates of plasma lipids and apolipoproteins were performed using an auto-analyzer. Genetic DNA was prepared from the blood clots using the Triton X-100 lysis technique. Amplification of a 432 bp fragment of the apoAI gene promoter was performed using PCR followed by restriction digestion, electrophoresis and identification of the genotypes involved. RESULTS: The samples were divided on the basis of alcohol consumption: non-drinkers, 1-25 g/day, 26-75 g/day and > 75 g/day. Comparing the four alcohol consumption groups, plasma HDLC and apoAI levels were increased as the alcohol consumption increased with no evidence of threshold effects in the Yi-farmers and the Han people groups. A similar association was found in the Yi-emigrant group, but was not statistically significant. The frequencies of the A allele in the three populations were similar, and no significant difference of lipid and apolipoprotein levels was found between subjects with and without the A allele in the three populations. But, in Han and Yi-emigrant samples, the drinkers with the GG genotype had higher plasma HDLC and apoAI levels than non-drinkers with the same genotype, while the drinkers with the A allele had lower plasma HDLC and apoAI levels than drinkers without the A allele. Non-drinkers with the A allele had higher levels of apoAI than non-drinkers with GG genotypes. It was estimated that 18% of the variability of plasma apoAI level could be explained by the G to A polymorphism in non-drinkers of Yi-emigrants (F = 8.94, P < 0.01). CONCLUSIONS: The present data suggest that moderate alcohol consumption and the G to A substitution could lower the risk of coronary heart disease (CHD), but the beneficial effects of one will be negated by the other.

Adolescent↗
PubMed1996

Increased prebeta-high density lipoprotein, apolipoprotein AI, and phospholipid in mice expressing the human phospholipid transfer protein and human apolipoprotein AI transgenes.

Human plasma phospholipid transfer protein (PLTP) circulates bound to high density lipoprotein (HDL) and mediates both net transfer and exchange of phospholipids between different lipoproteins. However, its overall function in lipoprotein metabolism is unknown. To assess the effects of increased plasma levels of PLTP, human PLTP transgenic mice were established using the human PLTP gene driven by its natural promoter. One line of PLTP transgenic mice with moderate expression of PLTP mRNA and protein was obtained. The order of human PLTP mRNA expression in tissues was: liver, kidney, brain, small intestine > lung > spleen > heart, adipose tissue. Western blotting using a human PLTP monoclonal antibody revealed authentic human PLTP (Mr 80 kD) in plasma. Plasma PLTP activity was increased by 29% in PLTP transgenic mice. However, plasma lipoprotein analysis, comparing PLTP transgenic mice to control littermates, revealed no significant changes in the plasma lipoprotein lipids or apolipoproteins. Since previous studies have shown that human cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase only function optimally in human apoAI transgenic mice, the human PLTP transgenic mice were cross-bred with human apoAI transgenic mice. In the human apoAI transgenic background, PLTP expression resulted in increased PLTP activity (47%), HDL phospholipid (26%), cholesteryl ester (24%), free cholesterol (37%), and apoAI (22%). There was a major increase of apoAI in prebeta-HDL (56%) and a small increase in alpha-HDL (14%). The size distribution of HDL particles within alpha- and prebeta-migrating species was not changed. The results suggest that PLTP increases the influx of phospholipid and secondarily cholesterol into HDL, leading to an increase in potentially antiatherogenic prebeta-HDL particles.

Animals↗