Distant supervision for cancer pathway extraction from text.

Biological pathways are central to understanding complex diseases such as cancer. The majority of this knowledge is scattered in the vast and rapidly growing research literature. To automate knowledge extraction, machine learning approaches typically require annotated examples, which are expensive and time-consuming to acquire. Recently, there has been increasing interest in leveraging databases for distant supervision in knowledge extraction, but existing applications focus almost exclusively on newswire domains. In this paper, we present the first attempt to formulate the distant supervision problem for pathway extraction and apply a state-of-the-art method to extracting pathway interactions from PubMed abstracts. Experiments show that distant supervision can effectively compensate for the lack of annotation, attaining an accuracy approaching supervised results. From 22 million PubMed abstracts, we extracted 1.5 million pathway interactions at a precision of 25%. More than 10% of interactions are mentioned in the context of one or more cancer types, analysis of which yields interesting insights.

Literome: PubMed-scale genomic knowledge base in the cloud.

MOTIVATION: Advances in sequencing technology have led to an exponential growth of genomics data, yet it remains a formidable challenge to interpret such data for identifying disease genes and drug targets. There has been increasing interest in adopting a systems approach that incorporates prior knowledge such as gene networks and genotype-phenotype associations. The majority of such knowledge resides in text such as journal publications, which has been undergoing its own exponential growth. It has thus become a significant bottleneck to identify relevant knowledge for genomic interpretation as well as to keep up with new genomics findings. RESULTS: In the Literome project, we have developed an automatic curation system to extract genomic knowledge from PubMed articles and made this knowledge available in the cloud with a Web site to facilitate browsing, searching and reasoning. Currently, Literome focuses on two types of knowledge most pertinent to genomic medicine: directed genic interactions such as pathways and genotype-phenotype associations. Users can search for interacting genes and the nature of the interactions, as well as diseases and drugs associated with a single nucleotide polymorphism or gene. Users can also search for indirect connections between two entities, e.g. a gene and a disease might be linked because an interacting gene is associated with a related disease. AVAILABILITY AND IMPLEMENTATION: Literome is freely available at literome.azurewebsites.net. Download for non-commercial use is available via Web services.

Two-year interim results from a 5-year study evaluating clinical recurrence of superficial basal cell carcinoma after treatment with imiquimod 5% cream daily for 6 weeks.

Imiquimod 5% cream is approved in the USA, Europe and Australia to treat superficial basal cell carcinoma, using a regimen of once daily, 5 times per week for 6 weeks. Vehicle-controlled, phase III clinical trials show that imiquimod is safe and effective for treating superficial basal cell carcinoma with dosing 5 or 7 times per week for 6 weeks. This phase III, open-label study evaluates the long-term (5 years) clinical efficacy and safety of dosing once daily, for which this manuscript reports the 2-year time point in the follow-up period. For the 169 enrolled subjects, the tumour selected for treatment was assessed clinically to determine initial clearance at the 12-week post-treatment visit. If clinically clear of superficial basal cell carcinoma, subjects entered a 5-year, long-term follow-up period. Subjects were evaluated for recurrence at the 3-, 6-, 12- and 24-month follow-up visits. The initial clearance rate at 12 weeks post treatment was 94.1%. The proportion of subjects who were clinically clear at the 2-year follow-up visit was estimated to be 82.0%. Imiquimod was tolerated when applied daily, with erythema reported for all subjects participating in the study. The recurrence rate observed suggests that once daily dosing and 5x/week dosing yield similar clearance rates, but daily dosing increases local skin reactions.

Successful treatment of in-transit melanoma metastases using topical 2-4 dinitrochlorobenzene.

A 78-year-old woman presented with multiple histologically proven in-transit melanoma metastases involving the lower half of the left leg. Initial therapy with liquid nitrogen cryotherapy had some short-lived success but was not tolerated by the patient. As further lesions began to develop, daily topical application of 2% 2-4 dinitrochlorobenzene to the lesions was commenced. During the first 2 years of therapy a partial response was achieved, with treated lesions regressing while new lesions developed. Eventually a long-term remission of almost 2 years with no clinical evidence of cutaneous melanoma deposits was achieved. This treatment did not prevent metastatic lymph node and ultimately fatal liver involvement. Topical immunotherapy can be a useful adjunct in the treatment of cutaneous melanoma metastases, particularly in those patients who are unable to tolerate other destructive modalities of therapy.