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liquid-biopsy

cfDNA cancer testing

Guardant360/Shield, GRAIL Galleri, Natera Signatera

SystemTechniques · 12Primitives · 40 liquid-biopsy Template enginescompilers · medium: Compile templates with loops, partials and auto-escaping into render functionsBayesian genotype likelihoodssearch-sort · medium: Per-site genotype likelihoods from read base qualities, combined with priors to call variantsExternal merge sortsearch-sort · medium: Sort data larger than RAM: write memory-sized sorted runs, then k-way merge them with large sequential buffers; terabytes in one merge pass.›Fm indexsearch-sort · medium: BWT plus rank structures for backward search: count and locate substrings in compressed spaceMultiplex pcr panel designsearch-sort · medium: Choose primer sets for many amplicons with melting-temperature windows, off-target checks and primer-dimer avoidanceSmith-Waterman local alignmentsearch-sort · medium: Dynamic programming that finds the highest-scoring pair of similar substrings of two sequences under a substitution score and affine gap penalties, in O(nm) time.›Umi duplex consensus callingsearch-sort · medium: Group reads by unique molecular identifier and strand, build per-family consensus, require both strands to suppress sequencing errorsVcf variant normalizationsearch-sort · low: Parse VCF and left-align/trim indels so equal variants share one representationBurrows-Wheeler transform (BWT)compression · low: Reversible permutation that sorts every character by the context following it, clustering equal bytes into runs; the core of bzip2 and of FM-index text search.›Edit distancesearch-sort · low: Levenshtein/Damerau distance by DP, bit-parallel Myers variantSeekable compressed streamcompression · low: Independently compressed blocks plus an index for random access (BGZF, seekable zstd, eStargz)Interval treedata-structures · low: Index of ranges that answers "which intervals overlap this point or range?" in O(log n + k); static sorted-array form is the compact, cache-friendly choice.›Union-findgraphs · low: Disjoint-set forest with union by size and path compression; merges sets and answers same-set queries in effectively constant time.›Calibrationmachine-learning · low: Make predicted probabilities match observed frequencies: measure with ECE, fix post hoc with temperature, Platt or isotonic scaling on held-out data.›Linear and logistic regressionmachine-learning · low: Fit a weighted sum of features to a number (least squares) or a probability (logistic); the baseline every model must beat.›Genomic binning indexsearch-sort · low: Hierarchical bin index (UCSC/tabix/BAI) for region queries over sorted genomic recordsDual control approvalsecurity · low: Four-eyes / maker-checker approval with quorum policies for sensitive operationsName resolutioncompilers · low: Bind every use of a name to its declaration with a scope stack, handling shadowing, hoisting and closure capture in one AST walk.›Recursive-descent parsingcompilers · low: Hand-written top-down parser with one function per grammar rule; simple, fast, with full control over error messages and recovery.›Html sanitizationsecurity · low: Allowlist-based HTML sanitizing of untrusted markupFloating-point errornumerics · low: How IEEE 754 rounding error accumulates and how to contain it: compensated (Kahan/Neumaier) and pairwise summation, error-free transformations with FMA, ULP comparisons.›Buffer pools for zero-allocation I/Ohardware-os · low: Preallocate a fixed set of aligned I/O buffers and recycle them through a free list, so the hot path never mallocs, faults or unmaps. The bounded count doubles as back pressure.›K way mergesearch-sort · low: Merge k sorted streams with a heap or loser tree (merging iterators)+ 5 more techniques+ 24 more primitives

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