标签：#bioinformatics

In bioinformatics we are handling a lot of tabular data. Be it VCF files, tabular Blast output, or just creating a CSV or TSV samplesheet. Actually, one of my favorite tabular formats is by using SeqKit to convert Fasta or FastQ files to tabular format, as this allows to do various filtering operations by row , using standard unix tools if so wished. Scrolling through this type of data in the terminal can be messy to say the least though. Although CSVs can of course be imported into a spreadsheet software for viewing, it would be very powerful to be able to view them comfortably right from the terminal, isn't it? To take one example that fits within the code window of a blog post, let's take a selected set of columns from the CSV output from the Mykrobe tool. And to make it emulate another common problem with many csv formats, let's also use tr to convert the _ :s in the headers into real spaces (Mykrobe does not do this, but many other tools do): $ cat SOME_SAMPLE.csv | cut -d , -f 2,3,10,14,15,17,18 | tr '_' ' ' > selection.csv $ cat selection.csv "drug" , "susceptibility" , "kmer size" , "phylo group per covg" , "species per covg" , "phylo group depth" , "species depth" "Amikacin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Capreomycin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Ciprofloxacin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Delamanid" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Ethambutol" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Ethionamide" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Isoniazid" , "R" , "21" , "99.672" , "98.428" , "372" , "347" "Kanamycin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Levofloxacin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Linezolid" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Moxifloxacin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Ofloxacin" , "S" , "21" , "99.672" , "98.428" , "372" , "347" "Pyrazinamide" , "S" , "21" , "99.672"

AI 工具整合評估報告 執行摘要 本報告評估了 7 個 AI 工具在臨床基因體學領域的應用潛力，重點測試了 3 個優先級最高的工具：MedGemma 醫療大語言模型、Nemotron RAG 文獻檢索系統，以及 Kimi K2.5 多模態視覺語言模型。 評估日期 : 2026-02-10 測試平台 : RTX 3090 24GB 評估目標 : 確認 AI 工具在變異解釋與臨床決策中的可行性 1. 測試項目總覽 1.1 優先級分類 P1 (高優先級) - 已評估: ✅ MedGemma - Google DeepMind 醫療大語言模型 ✅ Nemotron RAG - NVIDIA 文獻檢索與知識整合 ✅ Kimi K2.5 - 月之暗面多模態視覺語言模型 P2 (中優先級) - 已規劃: 📋 Gemini CLI Hooks - 工作流自動化 📋 DaGGR - Hugging Face 基因體學工具 📋 評測方法論 - 醫療 AI 評估框架 P3 (低優先級) - 待調研: 📋 OpenEvidence - 臨床證據檢索引擎 2. MedGemma 醫療大語言模型 2.1 工具概述 開發者 : Google DeepMind 基礎模型 : Gemma 7B 特化領域 : 醫療問答、臨床決策支持 技術規格 : { "model_size" : "7B parameters" , "quantization" : "8-bit (optional)" , "gpu_requirement" : "12-16GB VRAM" , "context_length" : "8192 tokens" , "languages" : "English (primary)" } 2.2 功能評估 核心能力 : 醫療知識問答 疾病症狀解釋 藥物機制說明 治療方案建議 基因變異解釋 基因功能說明 變異影響評估 臨床意義解讀 文獻摘要生成 PubMed 摘要 臨床指南解讀 研究結果總結 2.3 應用場景 場景 A: 變異臨床意義解讀 # 輸入 query = """ 變異資訊: - 基因: BRCA1 - 位置: chr17:41234470 - 變化: c.5266dupC (p.Gln1756Profs*74) - 類型: Frameshift 請解釋此變異的臨床意義。 """ # MedGemma 輸出 (預期) """ BRCA1 c.5266dupC 變異分析: 1. 變異類型: Frameshift insertion - 導致讀框位移 - 產生提前終止密碼子 (位置 1756+74) 2. 基因功能影響: - BRCA1 是腫瘤抑制基因 - 參與 DNA 雙鏈斷裂修復 - Frameshift 導致功能喪失 3. 臨床意義: - 致病性: Pathogenic (高可信度) - 疾病風險: 遺傳性乳腺癌/卵巢癌 (HBOC) - 乳癌風險: 55-72% (終生風險) - 卵巢癌風險: 39-44% 4. 臨床建議: - 遺傳諮詢 - 加強監測 (MRI + 超音波) - 考慮預防性手術 - PARP 抑制劑治療 (若已診斷) """ 場景 B: 醫療文獻查詢 query = " What are the latest treatments for TP53-mutated cancers? " # MedGemma 回答 (模擬) """ TP53 突變癌症的最新治療策略: 1. 標靶治療: - APR-246/Eprenetapopt: 恢復 TP53 功能 - PRIMA-1/APR-246: 臨床試驗進行中 2. 免疫治療: - PD-1/PD-L1 抑制劑 - TP53 突變可能影響免疫反應 3. 合成致死策略: - PARP 抑制劑 (部分 TP53 突變) - ATR/CHK1 抑制劑 4. 臨床試驗: - NCT02999893: APR-246 + 化療 - NCT03745716: TP53 疫苗免疫治療 """ 2.4 部署考量 技術需求 : GPU記憶體: 12-16GB (FP16) 或 8GB (INT8) 推理延遲: 2-5 秒/查詢 API 或本地部署均可 整合方案 : # 與變異註釋流程整合 def annotate_with_medgemma ( variant ): # 1. 提取變異資訊 gene = variant [ ' gene ' ] change = variant [ ' protein_change ' ] # 2. 生成查詢 prompt = f " Explain the clinical significance of { gene } { change } " # 3.

Alzheimer's disease affects over 55 million people worldwide, yet the precise molecular changes happening inside individual brain cells remain poorly understood. I wanted to dig into that question - not at the tissue level, but at single-cell resolution. So I built a full scRNA-seq analysis pipeline in Python using Scanpy, working with a publicly available dataset of 63,608 nuclei from human prefrontal cortex tissue (sourced from CZ CELLxGENE). The donors spanned three Braak stages: 0 (cognitively normal), 2 (early Alzheimer's), and 6 (severe Alzheimer's). Here's what I found and how I found it. The Dataset The data came from a study on the molecular characterisation of selectively vulnerable neurons in AD. It covers the superior frontal gyrus, a prefrontal region known to be hit hard by neurodegeneration - and includes seven major brain cell types: Glutamatergic neurons GABAergic neurons Oligodendrocytes OPCs (oligodendrocyte precursor cells) Astrocytes Microglia Endothelial cells 31,997 genes. 63,608 cells. Three disease stages. A lot to work with. The Pipeline 1. Quality Control No dataset is clean out of the box. I filtered cells to keep only those with between 200 and 6,000 detected genes, and excluded anything with more than 20% mitochondrial gene content (high mitochondrial reads usually signal a dying or damaged cell). This removed around 2,809 low-quality cells. 2. Normalisation Library sizes were normalised to 10,000 counts per cell, followed by log1p transformation, standard practice that makes cells comparable regardless of how deeply they were sequenced. I then identified 5,607 highly variable genes to focus the downstream analysis. 3. Dimensionality Reduction PCA (50 components) → neighbourhood graph (10 neighbours, 20 PCs) → UMAP embedding. The UMAP is where the biology starts to become visible. All seven cell types separated into distinct clusters, with clear separation between neuronal subtypes and glial populations. 4. Differential Expression For t