Haplotypic information in diploid organisms provides valuable information on human evolutionary history and plays an important role in identifying a candidate gene in the etiology of complex genetic diseases. However, haplotypes of diploid individuals cannot be acquired easily. Molecular haplotyping methods are very costly and have low throughput, and current genotyping and sequencing methods do not provide information on the linkage phase in diploid organisms. The application of statistical methods to infer the haplotype phase in samples of diploid sequences is a very cost-effective approach. Several computational and statistical methods have been developed for haplotype inference, including Clark's algorithm [1], the Expectation Maximization (EM) algorithm [2], and Gibbs sampler [3]. Because of its interpretability and stability, the EM algorithm has become one of the most widely used statistical algorithms. However, the standard EM algorithm has several weaknesses, including the inability to handle a large number of markers and convergence to the local optimum. To overcome these problems, various derivative methods have been developed, such as the Partition-Ligation EM (PLEM) algorithm to handle many more linked loci [4], the Optimal Step Length EM (OSLEM) algorithm to accelerate the calculations [5], and the Stochastic EM (SEM) algorithm to deal with missing genotypic data and to avoid convergence to local maxima [6]. However, most packages are intended for use with single-nucleotide polymorphism (SNP) data in a biallelic manner.More and more researchers are analyzing both multiallelic and biallelic markers in the linkage and/or association studies of complex diseases. The analysis of linkage disequilibrium (LD) between multiallelic loci and haplotype inference of many loci (including bi-and multiallelic markers) present a number of common problems. The major difficulty for the haplotype inference problem npg

Background: B-cell maturation antigen (BCMA) is a tumour necrosis superfamily cell-surface receptor required for plasma cell survival. This study evaluated safety, tolerability and preliminary clinical activity of GSK2857916, a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin-F, in patients with relapsed/refractory multiple myeloma (MM). Methods: This international, multicentre, open-label, first-in-human Phase 1 study comprised dose escalation (Part 1) and dose expansion (Part 2) phases. Adults with histologically or cytologically confirmed MM, Eastern Cooperative Oncology Group performance status 0/1, and progressive disease following stem cell transplant, alkylators, proteasome inhibitors and immunomodulators were recruited. In Part 1, patients received GSK2857916 (0 03–4 6 mg/kg) via 1-hour intravenous infusion. In Part 2, patients received the selected dose of GSK2857916 (3 4 mg/kg) every 3 weeks. Primary endpoints were maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). All patients who received ≥1 dose were included in this prespecified administrative interim analysis (cut-off: 26 June 2017), which was performed for internal purposes. The study is ongoing (NCT02064387). Findings: Between July 2014 and February 2017, 73 patients were treated (Part 1 n=38; Part 2 n=35). No MTD was identified in Part 1. Based on safety/clinical activity, 3 4 mg/kg was selected as RP2D. Corneal events were common (42/73; 58%); most (37/42) were Grade 1/2 and did not result in treatment discontinuation in Part 2. The other most common Grade 3/4 events were thrombocytopenia (25/73; 34%) and anaemia (11/73; 15%). There were 12 treatmentrelated serious adverse events and no treatment-related deaths. Overall response rate at 3 4 mg/kg in Part 2 was 60% (21/35; 95% confidence interval: 42 1%–76 1%). Interpretation: At the identified RP2D, GSK2857916 is well tolerated and data suggest it has good clinical activity in heavily pretreated patients, thereby indicating that this may be a promising candidate for the treatment of relapsed/refractory MM. Funding: GlaxoSmithKline plc