Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A systematic review of margin status in retroperitoneal liposarcomas: does the R0 margin matter?

Retroperitoneal liposarcomas (RPLPSs) are a rare tumor group for which current guidelines recommend aggressive en bloc resection to attain microscopically negative (R0) margins. To ensure R0 margins, resection of adherent or adjacent organs is often required. However, it is still unclear if R0 margins confer any additional benefit to patients over a grossly negative but microscopically positive (R1) margin. We performed a systematic search of PubMed and Embase databases for studies including patients receiving R0 or R1 resection for RPLPS. Nine retrospective cohort studies, one prospective cohort study, and 49 case reports/case series were included. A total of 552 patients with RPLPS were evaluated: 346 underwent R0 resection and 206 underwent R1 resection. In the R0 group, 5-year overall survival (OS) ranged from 58.3% to 85.7%; local recurrence (LR) ranged from 45.5% to 52.3%. In the R1 group, 5-year OS ranged from 35% to 55.3%; LR ranged from 66.7% to 91.7%. Among cohort studies, OS, disease-free survival (DFS), LR rate, and LR-free survival (LRFS) were significantly associated with R0 resections. Assessment of case series and reports suggested that the R0 margin led to a slightly higher morbidity than that of R1. In conclusion, this review found the R0 margin to be associated with reductions in LR rates and improved OS when compared with the R1 margins, though accompanied by slight increases in morbidity. The roles of tumor histotype and perioperative chemotherapy or radiotherapy were not well-elucidated in this review.Published versionThis study is supported by the NCCS Cancer Fund (Research) and SingHealth Duke-NUS Academic Medicine Centre, facilitated by Joint Office of Academic Medicine (JOAM). C-AJO is supported by the National Research Council Clinician Scientist-Individual Research Grant (CIRG21jun-0038). All the funding sources had no role in the study design, data interpretation or writing of the manuscript

Novel use of natural language processing for registry development in peritoneal surface malignancies

Background: Traditional methods of research registry development for rare conditions such as peritoneal surface malignancies (PSM) are often hindered by poor patient accrual and need for significant manpower resources. We develop a novel pipeline using natural language processing (NLP) to accelerate this process and demonstrate its real-world application in the identification of PSM patients, as well as characterisation of referral patterns in this cohort. Materials and methods: A training set comprising 100 radiological reports of abdomen and pelvis computed tomography scans was used to develop a rule-based NLP system able to classify reports based on the presence or absence of PSM. The algorithm was applied to a test set of 10,261 reports to identify all patients with PSM for registry creation. The registry was subsequently linked to electronic medical records, and the referral patterns of patients evaluated. Results: The algorithm identified 251 reports as positive for PSM from a total of 10,261 reports, of which 239 were concordant with manual review. Performance was excellent with a specificity of 90%, positive predictive value of 95%, and accuracy of 96%. From these, 228 unique patients were identified for registry inclusion after corroboration with pathological findings. Only 27.6% of patients were found to have been referred to and reviewed by PSM specialist surgeons. For those without a PSM specialist consult, 39.4% were managed by medical oncology, 11.5% by colorectal surgery, 7.3% by gastroenterology, 5.4% by internal medicine, and 29.1% by various other miscellaneous medical and surgical subspecialties. Conclusion: NLP is a useful tool in automated pipelines that can greatly contribute to registry creation, as well as research and quality improvement efforts