Development Of Reliable Biomarkers Research Articles

PredicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases.

Time-to-event prediction is a key task for biological discovery, experimental medicine, and clinical care. This is particularly true for neurological diseases where development of reliable biomarkers is often limited by difficulty visualising and sampling relevant cell and molecular pathobiology. To date, much work has relied on Cox regression because of ease-of-use, despite evidence that this model includes incorrect assumptions. We have implemented a set of deep learning and spline models for time-to-event modelling within a fully customizable 'app' and accompanying online portal, both of which can be used for any time-to-event analysis in any disease by a non-expert user. Our online portal includes capacity for end-users including patients, Neurology clinicians, and researchers, to access and perform predictions using a trained model, and to contribute new data for model improvement, all within a data-secure environment. We demonstrate a pipeline for use of our app with three use-cases including imputation of missing data, hyperparameter tuning, model training and independent validation. We show that predictions are optimal for use in downstream applications such as genetic discovery, biomarker interpretation, and personalised choice of medication. We demonstrate the efficiency of an ensemble configuration, including focused training of a deep learning model. We have optimised a pipeline for imputation of missing data in combination with time-to-event prediction models. Overall, we provide a powerful and accessible tool to develop, access and share time-to-event prediction models; all software and tutorials are available at www.predictte.org.

Cerebral amyloid angiopathy (CAA) in dementia cohort‐ biomarkers

AbstractBackgroundCerebral amyloid angiopathy (CAA) defined as deposition of amyloid β‐protein (Aβ) in brain vessels, leads to hemorrhagic phenomena and cognitive impairment. As a disease with Aβ deposition, CAA is commonly compared to Alzheimer’s disease (AD). Imaging‐based Boston criteria allow a diagnosis of probable CAA in vivo, but cannot predict the development of CAA thus development of reliable biomarkers is necessary.Recognizing the potential risks of CAA in patients with dementia is of great importance in the context of emerging accessibility of anti‐Aβ immunotherapy. Clinicians will be balancing the risks and benefits of such therapy for their Patients with Alzheimer’s disease on daily basis. This situation calls for developing better biomarkers of cerebral amyloid angiopathy.MethodPresented here a retrospective cohort study of 463 bio‐banked patients with cognitive disorders. De‐identified parameters like sex, age, MOCA, APOE; CSF levels: Aβ 1‐40, Aβ 1‐42, p and t Tau were correlated with the signs of CAA (as assessed by MRI).ResultsCAA was present in 53 out of 463 (11.5%) of the examined population with different types of dementia. 33% of those with CAA were diagnosed with Alzheimer’s disease; 38% with Vascular dementia;23% with MCI‐amnestic; 4% with MCI‐non‐amnestic; 2% with Lewy Body Dementia. Age and level of Amyloid beta 1‐40 were significantly associated with the occurrence of CAA, . An increase in age will increase the odds of developing CAA. From all the other parameters analyzed, the odds of CAA were linked to the low CSF level of Amyloid beta 1‐40.ConclusionLow CSF level of Amyloid beta 1‐40 may be considered a biomarker of CAA in dementia.

Prognostic and Predictive Biomarkers in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy-A Systematic Review.

Background: Radiotherapy is a mainstay in head and neck squamous cell carcinoma (HNSCC) treatment but is mostly applied without stratification by molecular diagnostics. Development of reliable biomarkers may have the potential to improve radiotherapy (RT) efficacy and reduce toxicity. We conducted a systematic review to summarize the field of biomarkers in HNSCC treated by RT. Methods: Pubmed and EMBASE were searched independently by two researchers following pre-defined inclusion and exclusion criteria. Z curves were generated to investigate publication bias. OncoKB was used for identification of druggable targets. Results: 134 manuscripts remained for data extraction. 12% of tumors were AJCC/UICC stage I-II and 82% were stage III-IV. The most common biomarkers were proteins (39%), DNA (14%) and mRNA (9%). Limiting analysis to prospective data and statistically significant results, we found three potentially druggable targets: ERCC2, PTCH1 and EGFR. Regarding data quality, AJCC/UICC stage was missing in 32% of manuscripts. 73% of studies were retrospective and only 7% were based on prospective randomized trials. Z-curves indicated the presence of publication bias. Conclusion: An abundance of potential biomarkers in HNSCC is available but data quality is limited by retrospective collection, lack of validation and publication bias. Improved study design and reporting quality might accelerate successful development of personalized treatments in HNSCC.

PUS1 is a novel biomarker for predicting poor outcomes and triple-negative status in breast cancer

Breast cancer patients' outcomes have improved dramatically in recent years, but relapses and poor prognosis remain common due to its aggressiveness and heterogeneity. The development of reliable biomarkers is still needed for predicting prognosis and treatment effectiveness. Recently, a growing body of research suggests that pseudouridine synthases contribute to the development of many cancers, but their contribution to breast cancer remains largely unknown. Using an integrative analysis, we selected pseudouridine synthase1(PUS1) as the candidate biomarker. A tissue microarray of 131 breast cancer patients was then utilized to determine the clinical significance and prognostic value of PUS1. RNA sequencing analysis was conducted to identify downstream genes that differ between control and PUS1 knockdown cells. The effect of PUS1 on phenotypes of cells was assessed using cell proliferation, colony formation, and transwell invasion assays. We found that breast tumors overexpressed PUS1 compared with paired normal tissues. PUS1 expression was positively correlated with triple-negative breast cancer (TNBC) status (P= 0.020) and tumor grade (P <0.0001), but not with age (P= 0.736), tumor size (P= 0.608), lymph node (P= 0.742), oestrogen receptor (ER) (P= 0.162), progesterone receptor (PR) (P= 0.901), human epidermal growth factor receptor 2 (HER2) (P= 0.608) or tumor stage (P= 0.411). Comparatively, patients with high PUS1 levels had shorter overall survival time (P=0.0001) and relapse-free survival time (P = 0.0093). A univariate and multivariate survival analysis suggested that the overall survival of patients was independently influenced by the PUS1 score (Univariate Cox P <0.0001, HR=5.176, 95% CI =2.420-11.07; Multivariate Cox P = 0.001, HR = 5.291, 95% CI =1.893-14.78). RNA sequencing data revealed the PUS1 knockdown significantly affects a series of cancer related biological process such as regulation of cell proliferation and cell migration, as well as KEGG pathways including Mitophagy and PI3K-Akt signaling. In vitro, knockdown of PUS1 significantly suppressed the proliferation and colony formation abilities of MDA-MB-231 cells and BT-549 cells. Additionally, the ability of tumor cells to invade was remarkably attenuated in low PUS1 expression groups compared with the corresponding control groups. Our results suggested that PUS1 is a novel biomarker that predicts poor outcomes in patients with breast cancer and may prove to be a promising treatment target.

Atopic Dermatitis: Striving for Reliable Biomarkers.

Atopic dermatitis (AD) is a highly heterogeneous inflammatory disease regarding both its pathophysiology and clinical manifestations. However, it is treated according to the “one-size-fits-all” approach, which may restrict response to treatment. Thus, there is an unmet need for the stratification of patients with AD into distinct endotypes and clinical phenotypes based on biomarkers that will contribute to the development of precision medicine in AD. The development of reliable biomarkers that may distinguish which patients with AD are most likely to benefit from specific targeted therapies is a complex procedure and to date none of the identified candidate biomarkers for AD has been validated for use in routine clinical practice. Reliable biomarkers in AD are expected to improve diagnosis, evaluate disease severity, predict the course of disease, the development of comorbidities, or the therapeutic response, resulting in effective and personalized treatment of AD. Among the studied AD potential biomarkers, thymus and activation-regulated chemokine/C-C motif ligand 17 (TARC/CCL17) has the greatest evidence-based support for becoming a reliable biomarker in AD correlated with disease severity in both children and adults. In this review, we present the most prominent candidate biomarkers in AD and their suggested use.

ABCC8 mRNA expression is an independent prognostic factor for glioma and can predict chemosensitivity

Glioma is the most common primary intracranial tumor and is associated with very low survival rates. The development of reliable biomarkers can help to elucidate the molecular mechanisms involved in glioma development. Here the expression of ABCC8 mRNA, clinical characteristics, and survival information based on 1893 glioma samples from four independent databases were analyzed. The expression patterns of ABCC8 mRNA were compared by a Chi square test. The overall survival rate of gliomas was evaluated according to the expression level of ABCC8 mRNA. The prognostic value of this marker in gliomas was tested using Cox single factor and multi factor regression analyses. We found patients with low WHO grade, oligodendrocytoma, low molecular grade, IDH mutation, and 1p19q combined deletion had high ABCC8 mRNA expression. The patients with high expression of ABCC8 mRNA had longer survival. ABCC8 mRNA expression was a new independent prognostic index for glioma. Temozolomide chemotherapy was an independent index to prolong overall survival in high ABCC8 mRNA expression glioma patients, whereas in patients with low expression, there was no significant difference. So ABCC8 mRNA expression could be an independent prognostic indicator for glioma patients and could predict the sensitivity of glioma to temozolomide.

Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay

Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void in objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested to determine concentrations of IL-19 serum levels, then correlated with the psoriasis activity and severity index (PASI) in psoriasis, and the eczema area and severity index (EASI) in atopic dermatitis. Not only was IL-19 increased in psoriasis and correlated to PASI, but ixekizumab administration led to rapid, sustained IL-19 decreases to normal levels, with decreases at 2-weeks correlating with PASI improvement at 16-weeks. IL-19 increased upon ixekizumab withdraw, prior to relapse, and decreased following re-treatment. In baricitinib- and etanercept-treated psoriasis patients, IL-19 decreases also correlated with improvement. Many patients with limited skin disease, including genital psoriasis and psoriatic arthritis patients, also had increased IL-19, which was reduced to normal levels upon ixekizumab treatment, correlating with PASI improvement. We also measured IL-19 in baricitinib-treated atopic dermatitis patients. In atopic dermatitis, IL-19 was significantly elevated, correlated with EASI scores, and decreased with skin improvement. Therefore, measurement of serum IL-19 provides clinicians with an objective disease-activity assessment tool for psoriasis and atopic dermatitis patients.

Type I Interferons in the Pathogenesis of Tuberculosis: Molecular Drivers and Immunological Consequences.

Tuberculosis (TB) remains a major global health threat. Urgent needs in the fight against TB include improved and innovative treatment options for drug-sensitive and -resistant TB as well as reliable biological indicators that discriminate active from latent disease and enable monitoring of treatment success or failure. Prominent interferon (IFN) inducible gene signatures in TB patients and animal models of Mycobacterium tuberculosis infection have drawn significant attention to the roles of type I IFNs in the host response to mycobacterial infections. Here, we review recent developments in the understanding of the innate immune pathways that drive type I IFN responses in mycobacteria-infected host cells and the functional consequences for the host defense against M. tuberculosis, with a view that such insights might be exploited for the development of targeted host-directed immunotherapies and development of reliable biomarkers.

Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports

Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites).Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery.Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73–0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04–0.22] and: 0.30; [95%CI: −0.03–0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing.In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved.

The CEECHE: a practical approach for reducing exposures and disease outcomes in Central and Eastern Europe.

While each region of the world faces unique challenges, environmental threats to vulnerable populations throughout Central and Eastern Europe (CEE) present a significant public health challenge. Environmental pollution is widespread, resulting from the consequences of rapid industrialization during the Soviet Union era. To help address these concerns, a meeting, sponsored in part by the National Institutes of Health (NIH)/National Institute of Environmental Health Sciences (NIEHS) Superfund Research Program (SRP), was convened in 1994. The meeting, "Hazardous Wastes - Exposure, Remediation, and Policy," brought together representatives of the governments of seven countries in the region, scientists from the United States and Western Europe, and representatives from international organizations to explore hazardous waste problems in the region. Since 1994, the SRP and partners have been holding meetings throughout CEE to share important information regarding environmental health. The general sessions have shifted from a focus on describing the problems in each country related to hazardous waste, exposure assessment, risk reduction, and risk communication, to an exchange of information to better define links between health and the environment and strategies to improve regional problems. The 1994 meeting and subsequent meetings raised issues such as heavy metal contamination, exposures from hazardous waste, and pollution caused by deficiencies in disposal of waste overall. Research priorities that were identified included development of reliable biomarkers, better understanding of the relationship between nutrition and chemical toxicity, more epidemiological studies in CEE, better methods of environmental data analysis, and development of remediation tools. Here, we review examples of research from current SRP grantees that address many of these issues. In 2004, the first official Central and Eastern European Conference on Health and the Environment (CEECHE) was held, and has been held biannually at venues across CEE. The CEECHE provides a forum for researchers and engineers, and organizations with diverse professional expertise and backgrounds, to jointly examine pressing environment and health issues, engage in cooperative research, and develop and disseminate innovative prevention strategies for addressing these issues. The CEECHE facilitates more intentional integration of disciplines to achieve a fundamental understanding of biological, environmental, and engineering processes and exploit this knowledge to contribute to solving environmental exposure-related issues. Critical to the CEECHE mission is the participation of trainees and junior scientists who will share their data and engage broadly with the scientific community. Scientific inquiry that supports a paradigm whereby knowledge gained through understanding disease processes resulting from environmental exposures would further our understanding of potential human health effects, and provide a creative, holistic approach to integrate seemingly discrete biological systems and geological, ecological and human health risk assessments into more comprehensive models. Such models will be discussed which advance the mission of reducing the public health burden of hazardous substances through interdisciplinary research and training.

Oxidative Stress in Kawasaki Disease Vasculitis

Although the underlying mechanisms by which Kawasaki disease (KD) triggers vasculitis remain unclear, certain stimuli that release inflammatory substances trigger vasculitis during its acute phase, and may continue to cause vascular deterioration in subsequent phases of this disease. Cellular systems responsible for the generation and scavenging of reactive oxygen species (ROS) are clearly involved in the pathogenesis of KD vasculitis. In this manuscript, we discuss studies that illuminate the role of exudative stress in vascular pathology occurring during the acute phase, the interval following the acute phase, and the chronic phase of KD. We also discuss appropriate therapies and the potential role of antioxidant therapy in the treatment and prevention of KD vasculitis. We conclude there is no clear evidence that current antioxidant therapy can prevent the onset of arteriosclerosis and that administering current antioxidant therapy to children with a prior history of KD may not immediately improve prognosis. Future prospects should include research on specifically targeted antioxidant treatments and the development of reliable biomarkers for assessing vascular oxidative stress.

Biomarker identification in psychiatric disorders: from neuroscience to clinical practice.

Patients with psychiatric disorders exhibit several neurobehavioral and neuropsychological alterations compared to healthy controls. However, signature endpoints of these behavioral manifestations have not yet been translated into clinical tests for diagnosis and follow-up measures. Recently, neuroproteomic approaches have been utilized to identify unique signature markers indicative of these disorders. Development of reliable biomarkers has the potential to revolutionize the diagnosis, classification, and monitoring of clinical responses in psychiatric diseases. However, the lack of biological gold standards, the evolving nosology of psychiatric disorders, and the complexity of the nervous system are among the major challenges that have hindered efforts to develop reliable biomarkers in the field of neuropsychiatry and drug abuse. While biomarkers currently have a limited role in the area of neuropsychiatry, several promising biomarkers have been proposed in conditions such as dementia, schizophrenia, depression, suicide, and addiction. One of the primary objectives of this review is to discuss the role of proteomics in the development of biomarkers specific to neuropsychiatry. We discuss and evaluate currently available biomarkers as well as those that are under research for clinical use in the future.

Cardiovascular Diseases Associated with Pregnancy: Early Assessment Using Non-Invasive MicroRNA Profiling

In some cases pregnancies are associated with severe cases of cardiovascular diseases (CVDs). The early detection and proper treatment of CVDs during maternity is detrimental to the health outcome and wellbeing of both mother and child. Unfortunately, both the detection rate and assessment of CVDs during pregnancies are unsatisfactory. Currently, the messenger RNA (mRNA) regulators called microRNAs (miRNAs) are being extensively profiled for use as clinical CVDs biomarkers due to their specific tissue and disease expression signature profiles. The identification and development of reliable biomarkers for early clinical assessment of CVDs during pregnancy could allow the detection of sub-clinical cardiac injury risk in vulnerable pregnant patients before irreversible damage occurs. CVDs specific miRNA biomarkers could provide the clinicians with a valuable tool to allow prognosis of patients at risk of cardiovascular injury and the introduction of therapy and intervention in order to increase health outcome and survival rate of both the mother and child.

Reproducibility of Magnetic Resonance Perfusion Imaging

Dynamic MR biomarkers (T2*-weighted or susceptibility-based and T1-weighted or relaxivity-enhanced) have been applied to assess tumor perfusion and its response to therapies. A significant challenge in the development of reliable biomarkers is a rigorous assessment and optimization of reproducibility. The purpose of this study was to determine the measurement reproducibility of T1-weighted dynamic contrast-enhanced (DCE)-MRI and T2*-weighted dynamic susceptibility contrast (DSC)-MRI with two contrast agents (CA) of different molecular weight (MW): gadopentetate (Gd-DTPA, 0.5 kDa) and Gadomelitol (P792, 6.5 kDa). Each contrast agent was tested with eight mice that had subcutaneous MDA-MB-231 breast xenograft tumors. Each mouse was imaged with a combined DSC-DCE protocol three times within one week to achieve measures of reproducibility. DSC-MRI results were evaluated with a contrast to noise ratio (CNR) efficiency threshold. There was a clear signal drop (>95% probability threshold) in the DSC of normal tissue, while signal changes were minimal or non-existent (<95% probability threshold) in tumors. Mean within-subject coefficient of variation (wCV) of relative blood volume (rBV) in normal tissue was 11.78% for Gd-DTPA and 6.64% for P792. The intra-class correlation coefficient (ICC) of rBV in normal tissue was 0.940 for Gd-DTPA and 0.978 for P792. The inter-subject correlation coefficient was 0.092. Calculated Ktrans from DCE-MRI showed comparable reproducibility (mean wCV, 5.13% for Gd-DTPA, 8.06% for P792). ICC of Ktrans showed high intra-subject reproducibility (ICC = 0.999/0.995) and inter-subject heterogeneity (ICC = 0.774). Histograms of Ktrans distributions for three measurements had high degrees of overlap (sum of difference of the normalized histograms <0.01). These results represent homogeneous intra-subject measurement and heterogeneous inter-subject character of biological population, suggesting that perfusion MRI could be an imaging biomarker to monitor or predict response of disease.

Circulating MACC1 Transcripts in Colorectal Cancer Patient Plasma Predict Metastasis and Prognosis

BackgroundMetastasis is the most frequent cause of treatment failure and death in colorectal cancer. Early detection of tumors and metastases is crucial for improving treatment strategies and patient outcome. Development of reliable biomarkers and simple tests routinely applicable in the clinic for detection, prognostication, and therapy monitoring is of special interest. We recently identified the novel gene Metastasis-Associated in Colon Cancer 1 (MACC1), a key regulator of the HGF/Met-pathway. MACC1 is a strong prognostic biomarker for colon cancer metastasis and allows identification of high-risk subjects in early stages, when determined in patients’ primary tumors. To overcome the limitation of a restricted number of molecular analyses in tumor tissue, the establishment of a non-invasive blood test for early identification of high-risk cancer patients, for monitoring disease course and therapy response is strongly needed.Methodology/Principal FindingsFor the first time, we describe a non-invasive assay for quantification of circulating MACC1 transcripts in blood of more than 300 colorectal cancer patients. MACC1 transcript levels are increased in all disease stages of the cancer patients compared to tumor-free volunteers. Highest MACC1 levels were determined in individuals with metastases (all P<0.05). Importantly, high MACC1 levels correlate with unfavorable survival (P<.0001). Combining MACC1 with circulating transcripts of the metastasis gene S100A4, a transcriptional target of the Wnt/β-catenin-pathway, improves survival prediction for newly diagnosed cancer patients.Conclusion/SignificanceThis blood-based assay for circulating MACC1 transcripts, which can be quantitated on a routine basis, is clinically applicable for diagnosis, prognosis, and therapeutic monitoring of cancer patients. Here we demonstrate the diagnostic and prognostic value of circulating MACC1 transcripts in patient plasma for metastasis and survival. Since MACC1 represents a promising target for anti-metastatic therapies, circulating MACC1 transcripts may prove to be an ideal read-out for monitoring therapeutic response of future interventions targeting MACC1-induced metastasis in cancer patients.

330 PREDICTIVE VALUE OF ERG PROTEIN EXPRESSION FOR DISEASE RECURRENCE AFTER RADICAL PROSTATECTOMY IN LOCALLY ADVANCED PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Prostate cancer remains the most common form of male cancer in US and Europe. Radical prostatectomy for locally advanced prostate cancer may produce acceptable oncological control of the disease and for selective group of patients can be sufficient. Despite that, prostate cancer exhibits considerable variability in clinical behavior, ranging from indolent to lethal disease. At present there is no means that can predict aggressive behavior of prostate tumors despite advances in biomarkers discovery based on proteomics, genomics and translational research. Thus, development of reliable biomarkers and a personalized clinical approach is critical in the management of clinically relevant disease. The objective of this study was to determine and correlate immunohistochemical ERG protein expression with clinic-pathological parameters using post prostatectomy tissue specimens and analyse its predictive value for disease recurrence in a well-designed locally advanced prostate cancer cohort. METHODS: 117 patients patient with locally advanced prostate cancer treated with radical prostatectomy, were inrolled prospective during 12 month (may 2010-apr 2011) Tissue microarray was done containing cores of all radical prostatectomy’s. Immunohistochemical expression of ERG was semi-quantitatively determined for all patients and then correlated with with prostatic specific antigen (PSA), Gleason Score (GS), pT-tumoral stage, surgical margins, biochemical recurrence and local recurrence. Period for follow-up was between 6-17 months. RESULTS: ERG expression was present in 67 patient (57.26%). ERG expression occurred more frequent in patient with PSA under 10ng/ml (p 0.0184). No significant relation between ERG expression and Gleason Score, pT stage and surgical margins was found. PSA at diagnosis (p 0.009), Gleason Score (p 0.00023), pT-stage (p 0.0001) and surgical margins (p 0.001), all had independent value in predicting biochemical disease recurrence. For locally disease recurrence positive surgical margins was the only independent predictor (p 0.0001). CONCLUSIONS: Immunohistochemical ERG protein expression does not have a predictive value for biochemical or local disease recurrence after radical prostatectomy in locally advanced prostate cancer.

Immunologic monitoring in transplantation revisited

Tailoring immunosuppressive drugs to an individual's needs is crucial to improve long-term outcomes of organ transplant patients. The purpose of this review is to summarize the data on promising biomarkers able to detect the risk of acute or chronic rejection and to discuss the potential issues for their implementation in the clinic. Multiple publications have indicated that circulating antibodies targeting human leukocyte antigen (HLA) and non-HLA antigens as well as donor-specific memory T cells are associated with accelerated graft failure. Other studies published within the year show that specific genomic and proteomic signatures obtained from urine, blood, and graft tissue correlate with acute rejection in kidney and heart transplant patients. The development of reliable biomarkers is crucial for individualizing therapy aimed at extending allograft survival and improving patient health. Emerging data indicate that monitoring assays, likely used in panels, have the potential to be diagnostic and possibly predictive of long-term outcome. In addition to ongoing discovery efforts, progress in the field will require multicenter validation, assay standardization, and commercialization so as to efficiently deliver reliable testing strategies to the practicing clinician.