Diagnostic signature challenge (DSC)

Psoriasis is the most prevalent autoimmune disease in the U.S; according to current studies, as many as 7.5 million Americans — approximately 2.2 percent of the population — have psoriasis. It is a chronic inflammatory and hyperproliferative skin disease, which, in addition to cutaneous manifestation, is accompanied with inflammatory arthritis in up to 40% cases.

The disease is diagnosed following physical examination of the skin lesions. Microscopic analysis of psoriatic skin biopsy shows thick, red, flaky cells with no sign of inflammation and blood tests can differentiate psoriasis from rheumatoid arthritis.

Psoriasis is typically treated with topical treatments of both steroids and non-steroids and phototherapy: UVB and UVA with light-sensitizing medication. There are also systemic medications and new drugs that target the autoimmune response and specific parts of the immune system (T cells, TNF, interleukin).

Clinical manifestation of psoriasis. (A) The red boxes show the most prevalent sites where psoriasis affects the skin. (B) Schematic view of the skin structure of a healthy and a psoriatic patient. Psoriatic skin shows signs of inflammation and scales (dead skin).

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system. The trigger of the autoimmune process in MS is unknown. MS is believed to occur as a result of some combination of genetic, environmental and infectious factors, and possibly other factors such as vascular problems. Previous studies of identical twins have demonstrated a concordance of 30% to develop MS, suggesting that the genetic background has a relatively limited but significant role in triggering MS.

The symptoms of the disease result from inflammation, swelling, and lesions on the myelin.

There are a number of MS progression subtypes (see Figure 1): relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). In 85% of the patients, the disease has a relapse-remitting (RR) course, which is characterized by the onset or deterioration of the neurological symptoms (relapses), followed by partial or complete recovery (remissions).

Similarly to most other autoimmune diseases, MS is significantly more common (at least 2-3 times) in women than men. This disease is most commonly diagnosed between the ages of 20 and 50. The risk of developing MS in the general population is 1/750 and over 2.5 million people are living with the disease worldwide. The disease can be managed and the symptoms controlled to various degrees of success with an individualized, multifaceted approach that includes medications and other therapies. However, there is no cure for multiple sclerosis.

Diagnosis by a neurologist usually involves ruling out other nervous system disorders with invasive and expensive tests such as lumbar puncture, Magnetic Resonance Imaging (MRI) brain scan and nerve function study.

Progression of the disease for clinically isolated syndromes and multiple sclerosis types. A clinically isolated syndrome (CIS) is an individual's first neurological episode, caused by inflammation or demyelination of nerve tissue. The diagnosis of multiple sclerosis is only possible after a MRI confirms lesions in the brain, which typically happens after multiple sites are affected (in the course of usually multiple events). The main forms of MS are distinguished by their different courses over time. RRMS is the most common form of MS. It defines patients having relapses followed by periods of remission. Multiple sclerosis diagnosis is made after a minimum of 2 relapses for RRMS. PPMS patients have constant symptoms without remission. SPMS progression starts the same way as RRMS, but at some point there is no more remission.

COPD encompasses chronic obstructive bronchiolitis with obstruction of small airways and emphysema with enlargement of airspaces and destruction of lung parenchyma, loss of lung elasticity, and closure of small airways. Although the disease is manifested in the small airways, the challenge is to produce a COPD signature that is valid in large airways where sample collection is easier to perform.

COPD causes a progressive airflow limitation that is not fully reversible and is associated with abnormal inflammatory responses to noxious particles or gases [1]. COPD is a major cause of chronic morbidity and mortality throughout the world with its prevalence being variable across different countries and groups. In developed countries smoking is a contributing factor to the disease.

As of 2011, COPD treatment was still in the active research and development phase. Pharmacotherapy decreased symptoms and complications and includes the use of long-acting bronchodilators and inhaled glucocorticosteroids. However, none of the existing medications offered a cure for or prevention of the long-term decline in lung function.

COPD is a disease that is manifested in the small airways. The challenge is to produce a COPD signature that is valid in large airways where sample collection is easier to perform.

COPD stages and symptoms

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) characterizes COPD patients into GOLD Stage 1-4 depending on the severity of disease (with GOLD Stage 4 being the most severe). Diagnosis is based on spirometry (a test which measures expiratory air flow) with or without a bronchodilator (to differentiate from asthma) and through questionnaires related to respiratory symptoms.

Historically, a GOLD Stage 0 characterized a higher risk population who did not present the clearer symptoms used to describe stage 1. Since not all of these patients will eventually develop COPD, we did not include them in this challenge. In addition, subjects that suffer from alpha1-antitrypsin deficiency represent a unique group of COPD patients and were also excluded.

In summary, the COPD phenotype refers to GOLD stages 1-4 while Controls are asymptomatic subjects that have no consistent symptoms.

In 2006 medical expenses from cancer care in the United States were an estimated $104.1 billion. As the population ages, costs are expected to continue to increase as cancer prevalence rises and expensive, targeted treatment strategies are becoming the standard of care. According to the World Health Organization (WHO) between 2004 and 2030, global cancer deaths will increase from 7.4 million to 11.8 million and cancer will be the leading cause of death followed by heart disease and stroke.

Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. NSCLC is divided into adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC) histologies.

NSCLC stage is generally defined by the TNM system. The T category describes the original (primary) tumor – tumor size and whether it has spread to surrounding tissue. The N category signifies any lymph node involvement (in and around the lungs), and the M category indicates whether the cancer has spread to other parts of the body, i.e. metastasized.

According to the overall TNM staging, stage 1 lung cancer is small and localized to only one area of the lung. Stage 2 and 3 cancers are larger and may have grown into the surrounding tissues and there may be cancer cells in the lymph nodes. Stage 4 cancer has spread to another body part.

Lung cancer subtypes. Distribution of lung cancer subtypes in a study with smoking status at the time of diagnosis. The pie chart shows the distribution of the non small cell lung cancer (NSCLC) subtypes: SCC (squamous cell lung cancer), AC (adenocarcinoma) and LCC (large cell lung cancer), and the small cell lung cancer (SCLC). The distribution of current (red) and former (green) smokers is shown as a histogram for each subtype. (B). Schematic of the tissues involved in squamous cell carcinoma and adenocarcinoma