Journal: bioRxiv

Article Title: High prevalence of CNS-directed autoantibodies in patients with schizophrenia

doi: 10.64898/2026.05.04.722731

Figure Lengend Snippet: A. Receiver Operator Classification (ROC) curve of the REAP-Lasso model for patient vs. control discrimination (AUC = 0.884). B. The number of common autoantibody (AAb) reactivities per individual by group (control, n=971; schizophrenia, n = 352). Common reactivities defined as present in >1% of the control cohort. Significance was assessed using unpaired two-sided Wilcoxon test. For the box plots, the central lines indicate the group median values, the top and bottom lines indicate the 75th and 25th percentiles, respectively, the whiskers represent 1.5× the interquartile range. C. The number of low-frequency autoantibody (AAb) reactivities per individual by group (control, n=971; schizophrenia, n = 352). Low-frequency reactivities defined as present in <= 1% of the control cohort. Significance was assessed using unpaired two-sided Wilcoxon test. For the box plots, the central lines indicate the group median values, the top and bottom lines indicate the 75th and 25th percentiles, respectively, the whiskers represent 1.5× the interquartile range. Low-freq = Low-frequency D. The number of autoantibody (AAb) reactivities against each tissue category per individual by group (control, n = 971; schizophrenia = 352). Tissue categories are composed of REAP reactivities bucketed by human protein atlas mRNA expression data. Significance was assessed by unpaired two-sided Wilcoxon with correction for multiple hypotheses by Benjamini-Hochberg. *** ∼ <0.001, ** ∼ <0.01, * ∼ <0.05. E, F. Forest plots depicting the top tissues (E) or single cell types (F) (y-axis) ranked by their estimated contribution to the overall schizophrenia vs. control increase in total autoantibodies (AAbs), with the x-axis reporting percentage of overall schizophrenia increase explained. Tissue or single cell categories are composed of REAP reactivities bucketed by human protein atlas mRNA expression data. Because a given protein may belong to more than one tissue class, percentages need not sum to 100. Closed circles (●) represent the observed percent contribution. Open circles (○) indicate the expected contribution under a REAP-library baseline. Horizontal whiskers denote 95% confidence intervals from a cohort-/group-stratified bootstrap that resamples subjects within schizophrenia and control groups (R = 4000 replicates).

Article Snippet: To assess whether specific tissues or cell types are preferentially targeted in schizophrenia, we annotated REAP antigens by tissue and cell-type expression using Human Protein Atlas (HPA) mRNA data.

Techniques: Control, Expressing, Single Cell

Journal: bioRxiv

Article Title: High prevalence of CNS-directed autoantibodies in patients with schizophrenia

doi: 10.64898/2026.05.04.722731

Figure Lengend Snippet: A. The number of autoantibody (AAb) reactivities against each tissue category per individual by group (control, n = 971; schizophrenia = 352). Single cell categories are composed of REAP reactivities bucketed by human protein atlas mRNA expression data. Significance was assessed by unpaired two-sided Wilcoxon with correction for multiple hypotheses by Benjamini-Hochberg. *** ∼ <0.001, ** ∼ <0.01, * ∼ <0.05.

Article Snippet: To assess whether specific tissues or cell types are preferentially targeted in schizophrenia, we annotated REAP antigens by tissue and cell-type expression using Human Protein Atlas (HPA) mRNA data.

Techniques: Control, Single Cell, Expressing

Journal: bioRxiv

Article Title: High prevalence of CNS-directed autoantibodies in patients with schizophrenia

doi: 10.64898/2026.05.04.722731

Figure Lengend Snippet: A. Conceptual figure for depiction of autoantibody odds ratio for schizophrenia status. B. Volcano plot depicting all autoantibody reactivities detected. Reactivities that are significantly enriched in schizophrenia (q-value <0.05, odds ratio (OR) >2.72) and target proteins with elevated expression in the brain and inhibitory and excitatory neurons by human protein atlas mRNA expression are bolded and colored. Color indicates functional annotation. Each dot represents one autoantibody reactivity. Vertical dashed lines indicate OR threshold +/-2.72. Horizontal dashed line indicates q-value threshold of 0.05. C. Conceptual figure for depiction of autoantibody odds ratio for schizophrenia status and AAb frequency in schizophrenia. D,E,F. Frequency plot depicting all autoantibody reactivities detected, with proteins belonging to the ion channel and Ca+2 excitability group (D) , synaptic function and synaptic plasticity groups (E) , and neuromodulatory GPCR (F) from figure B bolded and colored. Horizontal dashed lines indicate OR threshold of +/-2.72. Each dot represents one reactivity. G. Volcano plot depicting all anti-pathogen reactivities detected. Reactivities that are significantly enriched in schizophrenia (q-value <0.05, odds ratio (OR) >2.72) are bolded and colored. Color indicates pathogen class annotation. Each dot represents one reactivity. Vertical dashed lines indicate OR threshold +/-2.72. Horizontal dashed line indicates q-value threshold of 0.05

Article Snippet: To assess whether specific tissues or cell types are preferentially targeted in schizophrenia, we annotated REAP antigens by tissue and cell-type expression using Human Protein Atlas (HPA) mRNA data.

Techniques: Expressing, Functional Assay

Journal: bioRxiv

Article Title: High prevalence of CNS-directed autoantibodies in patients with schizophrenia

doi: 10.64898/2026.05.04.722731

Figure Lengend Snippet: A. Volcano plot depicting all autoantibody reactivities detected, with reactivities that are significantly enriched in schizophrenia (q-value <0.05, odds ratio (OR) >2.71) and target proteins elevated in brain pericytes, endothelial cells, astrocytes, vascular associated smooth muscle, or choroid plexus epithelial cells (by HPA mRNA expression data) bolded and colored. Each dot represents one autoantibody reactivity. Vertical dashed lines indicate OR threshold +/-2.71. Horizontal dashed line indicates q-value threshold of 0.05. B. Graphic representation of the MIMETAS chip used for the 3D human BBB model with flow. C. Diagram illustrating the creation of the 3D human BBB model and experimental scheme for the tracer permeability assay. D. Graphic representation of the experimental scheme for the TEER measurement with the OrganoTEER instrument. E. Graph of the TEER measurements over time in the 3D human BBB model under three conditions. Each dot represents one measurement. ** p<0.01, **** p<0.001. F. Representative images of tracer leakage from the blood (left) into the brain (right) compartment of the 3D BBB model. Biocytin is in green and Dextran is in red. There is increased tracer in the brain compartment with the BBB positive sera from Schizophrenia patients. G,H. Plots of the normalized signal of biocytin (G) and 70 KDa Dextran (H) permeability measurements at 30 minutes after tracer application. Significance was assessed using one way ANOVA (p=3.2E-9, 2.6E-12) followed by Tukey’s post hoc test. For the box plots, the central lines indicate the group median values, the top and bottom lines indicate the 75th and 25th percentiles, respectively, the whiskers represent 1.5× the interquartile range. BBB = Blood brain barrier. I. Number of autoantibodies (AAb) per individual (ID) targeting proteins with elevated expression in the brain by human protein atlas mRNA expression data. N=328 for BBB-, 24 for BBB+. Significance was assessed using unpaired Wilcoxon. For the box plots, the central lines indicate the group median values, the top and bottom lines indicate the 75th and 25th percentiles, respectively, the whiskers represent 1.5× the interquartile range. BBB = Blood-brain barrier.

Article Snippet: To assess whether specific tissues or cell types are preferentially targeted in schizophrenia, we annotated REAP antigens by tissue and cell-type expression using Human Protein Atlas (HPA) mRNA data.

Techniques: Expressing, Permeability

Journal: Gastro Hep Advances

Article Title: Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH

doi: 10.1016/j.gastha.2025.100745

Figure Lengend Snippet: Validation of AB4 for IHC using human spleen (KLB-negative) and liver tissue (KLB-positive). KLB protein expression in (A) human spleen tissue with (B) negative control and (C) human liver tissue with (D) negative control. Scale bars represent 200 μm.

Article Snippet: Although KLB protein expression data are available in the Human Protein Atlas database [dataset] , the employed antibody has been scored as uncertain for immunoblotting and IHC.

Techniques: Biomarker Discovery, Expressing, Negative Control

Journal: Gastro Hep Advances

Article Title: Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH

doi: 10.1016/j.gastha.2025.100745

Figure Lengend Snippet: KLB protein expression levels using AB4 and CK19 in human and monkey tissues. KLB protein expression levels in (A) human liver (200 μm) with (B) negative control (200 μm), (C) human bile ducts in liver (80 μm) with (D) CK19 staining as positive control (80 μm), (E) monkey liver (90 μm) with (F) negative control (90 μm), (G) human gallbladder (200 μm) with (H) negative control (200 μm) and (I) CK19 staining as positive control (300 μm).

Article Snippet: Although KLB protein expression data are available in the Human Protein Atlas database [dataset] , the employed antibody has been scored as uncertain for immunoblotting and IHC.

Techniques: Expressing, Negative Control, Staining, Positive Control

Journal: Gastro Hep Advances

Article Title: Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH

doi: 10.1016/j.gastha.2025.100745

Figure Lengend Snippet: KLB protein expression levels using AB4 along the human gastrointestinal tract. KLB protein expression levels in (A) human stomach (200 μm) with (B) negative control (200 μm), and (C) human colon tissue (90 μm) with (D) negative control (90 μm).

Article Snippet: Although KLB protein expression data are available in the Human Protein Atlas database [dataset] , the employed antibody has been scored as uncertain for immunoblotting and IHC.

Techniques: Expressing, Negative Control

Journal: Gastro Hep Advances

Article Title: Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH

doi: 10.1016/j.gastha.2025.100745

Figure Lengend Snippet: KLB protein expression levels using AB4 in human adipose tissue and pancreas. KLB protein expression levels in (A) human adipose tissue with (B) negative control, and (C) human pancreas with (D) negative control and (E) insulin staining as positive control to visualize the islets of Langerhans. Scale bars represent 200 μm.

Article Snippet: Although KLB protein expression data are available in the Human Protein Atlas database [dataset] , the employed antibody has been scored as uncertain for immunoblotting and IHC.

Techniques: Expressing, Negative Control, Staining, Positive Control

Journal: Gastro Hep Advances

Article Title: Beta-Klotho Protein Expression in Healthy Human Tissues and Liver Biopsies From Patients With MASLD or MASH

doi: 10.1016/j.gastha.2025.100745

Figure Lengend Snippet: Quantified KLB protein levels using AB4 in liver biopsies of patients with varying stages of MASLD (n = 28). (A) Overview of patient liver biopsies with MASLD stained with AB4, separated into different fibrosis grades. (B and C) Association of KLB protein expression levels with typical MASLD characteristics, specifically (B) lobular inflammation (Kruskal–Wallis, P = .0168), (C) portal inflammation (Kruskal–Wallis, P = .0809), (D) fibrosis grade (Kruskal–Wallis, P = .6602), (E) steatosis grade (Kruskal–Wallis, P = .7834), and (F) ballooning (Kruskal–Wallis, P = .1097).

Article Snippet: Although KLB protein expression data are available in the Human Protein Atlas database [dataset] , the employed antibody has been scored as uncertain for immunoblotting and IHC.

Techniques: Staining, Expressing

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: LRIG1 mRNA expression in normal human tissues. (A) Genomic structure of human LRIG1-3 . The human LRIG1 gene, located on Chr3q14, spans 122,136 bp and consists of 19 exons. The LRIG2 and LRIG3 genes are smaller than the LRIG1 gene. The sizes of exons and introns are not drawn to scale. (B) Schematic of the human LRIG1 protein structure. SP, signal peptide; LRR, leucine-rich repeat; LRRNT, LRR N-terminal flanking; LRRCT, LRR C-terminal flanking; TM, transmembrane. Shown below are several commonly used anti-LRIG1 antibodies (mAb, monoclonal antibody; pAb, polyclonal antibody). (C) Sequence logos for human LRIG1 LRR amino acid alignments. (D) Heat map of LRIG1 , LRIG2 and LRIG3 mRNA levels from GTEx. (E) Heat map presentation of the relative LRIG1 protein expression levels in human normal tissues based on immunohistochemistry staining (using the HPA011846; B) in samples from 44 normal tissue types of 144 individuals in the Human Protein Atlas. The box colors, dark blue, medium blue, blue and light blue, respectively, represent the “High, Medium, Low, Not Detected’ expression levels of the LRIG1 protein, as indicated on the top of the heat map.

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing, Sequencing, Immunohistochemistry, Staining

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) Low levels of LRIG1 mRNA expression in most cultured human cancer cell lines. Gene expression data was extracted from the CCLE Cancer Cell Line Encyclopedia ( https://portals.broadinstitute.org/ccle ). Shown are the violin plots of the LRIG1 mRNA levels (RSEM) in the indicated cancer cell types (n indicated in parentheses). Median and quartiles as indicated. Each dot represents an individual cell line. (B) Heat map of LRIG1 protein expression in the indicated human cancers. The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number). ND, not detected. The numbers in individual boxes represent the number of cases. Note that the majority of patient tumors expressed undetectable LRIG1 protein with the glioma as an exception. (C) LRIG1 mRNA expression is decreased in colorectal and thyroid cancers but increased in glioma and thymoma. Shown are the box plots of LRIG1 mRNA levels in tumor samples from TCGA and combined normal tissues from TCGA and GTEx ( http://gepia.cancer-pku.cn ). *p < 0.05 (ANOVA). (D) Increased LRIG1 mRNA levels in human PCa. Shown are LRIG1 mRNA levels in two different tumor-normal comparisons from the TCGA-PRAD dataset. ****p < 0.0001 (paired Student’s t -test). (E) In TCGA-PRAD dataset, LRIG1 mRNA levels are increased in PCa of all Gleason (G) grades compared to normal (N). p < 0.001 (paired Student’s t -test). However, LRIG1 mRNA levels gradually declined accompanying the increased tumor grade. p < 0.0001 (Jonckheere-Terpstra test).

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing, Cell Culture, Gene Expression, Immunohistochemistry, Staining

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) WB of LRIG1 in lung cancer cells. A549, H460 and H1299 cells infected with pLVX-LRIG1 (LRIG1) or empty control (EV) lentivirus were used to prepare whole cell lysate in WB analysis of LRIG1 (a mAb against LRIG1 was used) and other proteins indicated. 293T-LRIG1 cells were used as positive control. Varying amounts of proteins were loaded in WB and GAPDH was used as a control. Note that that these 3 lung cancer cell lines do not express detectable endogenous LRIG1 and also lacked appreciable expression of ERBB2/ERBB3. (B) Clonal assays in H460 cells infected with pLVX-LRIG1 lentivirus (LRIG1) and the control empty lentivirus (EV) for 72 h and plated in 6-well plates (300 cells/well). Clones were counted 13 days after plating. Presented are the mean ± SD from triplicate cells. **p < 0.01 when compared with the corresponding EV controls (paired Student’s t -test). Shown on the right are representative images of the clones. (C-D) LRIG1 expression inhibits lung cancer xenograft growth. Shown in C are the tumor images and tumor incidence (# tumors/# injections), endpoint tumor weights (mean ± S.D) and the corresponding p-value (Student’s t -test). Shown in D is the boxplot of tumor weights (***p < 0.001).

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Over Expression, Infection, Control, Positive Control, Expressing, Clone Assay

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) Contrasting mRNA expression patterns between LRIG1 and MYC and between LRIG1 and LRIG3 in normal human prostate (NHP) luminal and basal cells. Shown are the mRNA levels (normalized read_counts) for the indicated genes based on our RNA-seq profiling data ( GSE67070 ). *p < 0.05 (paired Student’s t -test). (B-F). LRIG1 mRNA levels are up-regulated in low grade prostate tumor tissues (L) compared with the matched normal tissues (N), but slightly downregulated in high grade tumor tissues (H) in 4 representative Oncomine datasets (B-E) and in TCGA (F). Similar trend was observed in some datasets with PSA (KLK3) and FKBP5 mRNA levels. Patient numbers are indicated. Note that the AR mRNA levels were elevated in only one dataset (D). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing, RNA Sequencing

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: LNCaP cells were infected with a doxycycline (DOX) inducible LRIG1-encoding lentiviral vector (MOI of 5) and selected with puromycin for ~2 weeks [ 100 ]. The LNCaP-LRIG1-puro cells were implanted subcutaneously (s.c) into two groups of male NOD/SCIDγ mice (12 mice/group), and, on day 35, one group of mice received DOX-supplemented chow (+DOX) and the other group the regular chow (−DOX). Tumor volumes were monitored and measured using a digital caliper and data presented in A (*p < 0.05; paired Student’s t -test). The experiment was terminated on day 52 and tumors harvested. Presented in B is the image of endpoint tumors with incidence and weights indicated. Note that the LRIG1-expressing tumors were nearly twice as smaller as the control (CTL) tumors (i.e., −DOX) although the p-value is not statistically significant due to big variations in tumor size.

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Infection, Plasmid Preparation, Expressing, Control

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) In normal prostate tissues, ERBB2 mRNA was expressed at highest levels followed by ERBB3 and EGFR while ERBB4 mRNA was barely detectable, and there was reasonable correlation between the ERBB2 and ERBB3 mRNA levels with LRIG1 . Pearson correlation coefficient for linear regression was calculated based on expression data of the 5 genes in 232 normal prostate tissues from the GTEx project, with R and p-value indicated. (B) In PCa, ERBB3 was expressed at the highest level and there was a significant correlation between ERBB3 mRNA levels with LRIG1 . Pearson correlation coefficient for linear regression was calculated based on expression data in 498 PCa samples from TCGA project, with R and p-value indicated.

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) Heterogeneous LRIG1 mRNA expression in CRPC. Shown are the relative LRIG1 mRNA levels in CRPC compared to corresponding hormone-naïve PCa in 3 Oncomine datasets. LRIG1 was upregulated in the Tomlins dataset (FC = 2.359; p = 0.009) and showed reduced trend in the Best dataset (FC= −1.635; p = 0.095) whereas LRIG1 did not change in Holzbeirlein dataset (FC = 1.029; p = 0.483). (B) Discordant LRIG1 and AR expression and persistently high LRIG1 expression in patient CRPC. Shown are matched IHC images of AR and LRIG1 in the whole-mount slides of 4 patient CRPC specimens (adapted with permission from [ 100 ]). Note that most CRPC cells lost AR expression but retained high levels of LRIG1. (C) Persistent LRIG1 expression in CRPC xenograft models. Whole cell lysates (60 μg/lane) prepared from 4 pairs of androgen-dependent (AD) and androgen-independent (AI; castration-resistant) xenograft tumors (lanes 1-8) and from 1 pair of in vitro castrated (i.e., CDSS for 48 h) LNCaP cells (lanes 9-10) were used in WB analysis of the molecules indicated. (D) Alterations of LRIG1 in an in vitro castration model. As detailed in [ 108 ], LNCaP cells were subjected to 3 regimens of long-term castration in culture, i.e., CDSS (charcoal dextran stripped serum), ENZA (enzalutamide; 10 μM), or CDSS plus bica (bicalutamide; 20 μM) for the time intervals indicated (w, week; m, month). Whole cell lysates (60 μg/lane) were used in WB analysis of the molecules indicated. *, cleaved ~110-kD and 100-kD LRIG1 ECD fragments. The arrow indicates the 60-kD ECD fragment.

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing, In Vitro

Journal: Seminars in cancer biology

Article Title: LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor

doi: 10.1016/j.semcancer.2020.12.016

Figure Lengend Snippet: (A) In PCa, oncogenic signaling from androgen/AR, ERBB/ligands and MYC induces LRIG1 expression and the upregulated LRIG1, in turn, antagonizes tumorigenesis driven by these pathways. Adapted with permission from [ 100 ]. (B) LRIG1 similarly functions as a feedback tumor suppressor in other ERBB-driven human cancers (see Text).

Article Snippet: The LRIG1 protein expression data was extracted from the Human Protein Atlas, based on immunohistochemistry staining of LRIG1 (HPA011846; see Fig. 1B ) in samples from 189 cancer patients of 19 different cancer types (total n indicated in parentheses, scale bar represents case number).

Techniques: Expressing